Nowadays, liver metastasis remains difficult to cure. When tumor cells escape and arrive in the liver sinusoids, they encounter the local defense mechanism specific to the liver. The sinusoidal cells have been widely ...Nowadays, liver metastasis remains difficult to cure. When tumor cells escape and arrive in the liver sinusoids, they encounter the local defense mechanism specific to the liver. The sinusoidal cells have been widely described in physiologic conditions and in relation to metastasis during the past 30 years. This paper provides an “overview” of how these cells function in health and in diseases such as展开更多
Liver transplantation is the optimal treatment for patients with end-stage liver disease,metabolic liver diseases,and hepatic malignancies that are not amenable to resection.Hepatic ischemia-reperfusion injury(IRI)is ...Liver transplantation is the optimal treatment for patients with end-stage liver disease,metabolic liver diseases,and hepatic malignancies that are not amenable to resection.Hepatic ischemia-reperfusion injury(IRI)is the main problem in liver transplantation and liver resection,leading to parenchymal cell injury and organ dysfunction.The damage of liver sinusoidal endothelial cells(LSECs)is a critical event in IRI.LSECs work as an important regulating factor of liver regeneration after partial hepatectomy.This review primarily describes the mechanisms of LSECs injury in IRI and explores the roles of LSECs in liver regeneration,and briefly introduces the protective strategies targeting LSECs damaged in IRI.展开更多
Hepatic stellate cells,hepatic sinusoidal endothelial cells and hepatic sinusoidal capllarization are closely related to the occurrence and progression of hepatic fibrosis.The pathological activation of hepatic stella...Hepatic stellate cells,hepatic sinusoidal endothelial cells and hepatic sinusoidal capllarization are closely related to the occurrence and progression of hepatic fibrosis.The pathological activation of hepatic stellate cels is the central link of hepatic fibrosis,and hepatic sinusoidal capillarization also promotes the occurrence and development of liver diseases.In the course of hepatic fibrosis,there is always a mutually reinforcing relationship between the activation of hepatic stellate cells and the capillarization of hepatic sinusoids.This paper strives to find an effective way to intervene or even reverse this vicious cycle by deeply investigating the effect of hepatic stellate cells and hepatic sinusoidal capillarization on hepatic fibrosis and their mutual promotion,and provide a new idea for the treatment of hepatic fibrosis,which is of great significance for relieving and reversing hepatic fibrosis.展开更多
Cirrhosis develops from liver fibrosis and is the severe pathological stage of all chronic liver injury. Cirrhosis caused by hepatitis B virus and hepatitis C virus infection is especially common. Liver fibrosis and c...Cirrhosis develops from liver fibrosis and is the severe pathological stage of all chronic liver injury. Cirrhosis caused by hepatitis B virus and hepatitis C virus infection is especially common. Liver fibrosis and cirrhosis involve excess production of extracellular matrix,which is closely related to liver sinusoidal endothelial cells(LSECs). Damaged LSECs can synthesize transforming growth factor-beta and platelet-derived growth factor,which activate hepatic stellate cells and facilitate the synthesis of extracellular matrix. Herein,we highlight the angiogenic cytokines of LSECs related to liver fibrosis and cirrhosis at different stages and focus on the formation and development of liver fibrosis and cirrhosis. Inhibition of LSEC angiogenesis and antiangiogenic therapy are described in detail. Targeting LSECs has high therapeutic potential for liver diseases. Further understanding of the mechanism of action will provide stronger evidence for the development of anti-LSEC drugs and new directions for diagnosis and treatment of liver diseases.展开更多
Important advances have been made in research into the mechanism of alcoholic liver disease (ALD) over the past few years,but the role of liver sinusoidal endothelial cell (LSEC) in ALD has not been elucidated adequat...Important advances have been made in research into the mechanism of alcoholic liver disease (ALD) over the past few years,but the role of liver sinusoidal endothelial cell (LSEC) in ALD has not been elucidated adequately. This study was undertaken to investigate the effect of ethanol on fenestrae of LSECs in rats. METHODS: A rat model of alcoholic liver disease was established by means of direct intragastric instillation of ethanol. Fifty-five rats of experimental (35 rats) and control (20) groups were sacrificed at the end of 4,8,12 weeks respectively, and also at the end of 12-week abstinence. After heart perfusion, the liver tissue was fixed and stained with hematoxylin and eosin for observation of serial changes of LSEC-fenestrae under a transmission electron microscope. RESULTS: Normal LESC was flat with a nucleus and organelles arranged regularly. The distal cytoplasm displayed as a lamina with many fenestrae, lacking the basement membrane(BM) underneath the endothelium. At the end of 4-week alcohol feeding, the number of fenestrae decreased at the distal cytoplasm in some LSECs, without the formation of the BM underneath the endothelium. At the end of 8 weeks, the number of fenestrae decreased significantly or even disappeared. The BM began to develop incompletely underneath the endothelium, while the active fibroblast appeared. At the end of 12 weeks, the number of fenestrae decreased more significantly and the complete BM could even be seen. But the changes were mostly limited in the single or adjoining sinus, and fibrosis was scarcely formed. At the end of 12-week abstinence, defenestration and formation of the endothelial BM lightened significantly. CONCLUSIONS:Defenestration and formation of the BM in LSECs develop gradually with the chronic stimulation of ethanol. Hepatic sinusoidal capillarization and fibrosis will be seen if their state is more serious. These early changes, i. e., limited and regional defenestration and capillarization may be the basis of alcoholic peri-fibrosis. This kind of he- patic fibrosis is reversible after removal of etiological factors.展开更多
OBJECTIVE To investigate the effect of co-culture between colon cancer cells （SW1116） and human liver sinusoidal endothelial cells （HLSECs） on cancer cell metastasis, and to provide a novel model for studying the ...OBJECTIVE To investigate the effect of co-culture between colon cancer cells （SW1116） and human liver sinusoidal endothelial cells （HLSECs） on cancer cell metastasis, and to provide a novel model for studying the mechanism of colon cancer liver metastasis. METHODS HLSECs and SW1116 were co-cultured for 21 rounds in vitro. Transwell migration, gelatin-zymography, CCK-8 proliferation and colony formation assays were used to examine the invasion, proliferation, and colony forming ability of cancer cells. Assays were carried out to examine tumor growth ability and liver metastasis. The associated molecular change was examined by western blotting. RESULTS After 21 selection rounds, colon cancer cells SWl 1161）21 displayed a clear boundary. Compared with the 5W1116 cells, SW1116P21 cells had a greater invasive ability, cell proliferation and colony formation in soft agar. A gelatin-zymography assay showed that the ability of SW1116P21 cells to secrete matrix metalloproteinase-2/9 was significantly greater than that of SWl116 cells. Additionally, the capacity for subcutaneous tumor formation of SW1116P21 was significantly increased. It was found that mice injected with SW1116P21 cells developed significantly more visually observable liver nodules than mice injected with SW1116 cells. Western blotting showed increased vimentin expression and decreased E-cadherin expression in the SW1116P21 cells, compared with the SWl 116 cells. CONCLUSION The interaction between SW1116 and HLSECs may promote tumor cell invasion, proliferation and colony formation in vitro, and tumor formation and liver metastasis in vivo. An epithelial-mesenchymal transition occurs in SWl 116P21 cells, which contributes to the change in the characteristics of tumor cells.展开更多
BACKGROUND The machine perfusion(MP)preservation including hypothermic MP(HMP)and midthermic MP(MMP)has been considered as a promising strategy to preserve the functions of liver donated after cardiac death.The import...BACKGROUND The machine perfusion(MP)preservation including hypothermic MP(HMP)and midthermic MP(MMP)has been considered as a promising strategy to preserve the functions of liver donated after cardiac death.The importance of understanding liver sinusoidal endothelial cells(LSEC)damage in regulating liver injury during MP has been emphasized.However,the ultrastructural changes in the LSEC and sinusoids around them after MP are unclear.AIM To investigate the ultrastructural changes in the LSEC and sinusoids around them after MP.METHODS Porcine liver grafts undergo a warm ischemia time of 60 minutes perfused for 4 h with modified University of Wisconsin gluconate solution.Group A grafts were preserved with HMP at 8℃ constantly for 4 h.Group B grafts were preserved with a rewarming solution at 22℃ by MMP for 4 h.Then the ultrastructural changes in the LSEC and sinusoids in Group A and B were comparatively analyzed by using osmium-maceration scanning electron microscopy with complementary transmission electron microscopy methods.RESULTS An analysis of the LSEC after warm ischemia revealed that mitochondria with condensed-shaped cristae,abnormal vesicles,reduction of ribosomes and the endoplasmic reticulum(ER)surround the mitochondria appeared.The MP subsequent after warm ischemia alleviate the abnormal vesicles and reduction of ribosomes in LSEC,which indicated the reduction of the ER damage.However,MMP could restore the tubular mitochondrial cristae,while after HMP the condensed and narrow mitochondrial cristae remained.In addition,the volume of the sinusoidal space in the liver grafts after MMP were restored,which indicated a lower risk of pressure injury than HMP.CONCLUSION MMP alleviates the ER damage of LSEC by warm ischemia,additionally restore the metabolism of LSEC via the normalization of mitochondria and prevent the share stress damage of liver grafts.展开更多
Hepatic sinusoidal endothelial cell(LSECs),as the sinusoidal capillary channel of the liver,is the most abundant non-parenchymal cell group in the liver. LSECs not only forms a barrier in the hepatic sinusoid,but also...Hepatic sinusoidal endothelial cell(LSECs),as the sinusoidal capillary channel of the liver,is the most abundant non-parenchymal cell group in the liver. LSECs not only forms a barrier in the hepatic sinusoid,but also has important physiological and immunological functions,including filtration,endocytosis,antigen presentation and leukocyte recruitment. It has been clear that LSECs play an important role in maintaining immune homeostasis in the liver and delaying the immune response to acute and chronic liver injury. In this review,we summarize how LSECs affect the immune microenvironment in the liver,and discuss their role in immune-mediated chronic liver disease,carcinogenesis,inflammation and aging process.展开更多
Objective:To observe the effect of Qishen decoction on dedifferentiation and autophagy of liver sinusoid endothelial cells(LSEC);Methods:LSEC were randomly divided into the control group,model group,Qishen Decoction l...Objective:To observe the effect of Qishen decoction on dedifferentiation and autophagy of liver sinusoid endothelial cells(LSEC);Methods:LSEC were randomly divided into the control group,model group,Qishen Decoction low,medium,high dose group,and inhibitor group.The model was induced by 100μg/ml oxidized low-density lipoprotein(oxLDL)for 24 hours,and the corresponding drugs or medicated serum were given for intervention.The expression levels of VEGFR2 and ET1 were detected by RT-qPCR and immunofluorescence staining,the ultrastructure of LSEC was detected by transmission electron microscopy,the content of NO was detected by ELISA,the expression levels of autophagy related proteins(LC3BI,LC3BⅡand p62)and endothelial function related proteins(eNOS and p-eNOS)were detected by western blot;Results:The results of transmission electron microscopy showed that Qishen decoction medicated serum could increase the number of fenestra and autophagy in LSEC cells,and inhibit the formation of basement membrane under endothelium.Compared with the model group,Qishen decoction medicated serum could significantly up-regulate the expression level of VEGFR2 mRNA and protein in LSEC,down regulate the expression level of ET1 mRNA and protein,the difference was statistically significant(P<0.05).In addition,Qishen decoction medicated serum could significantly increase the expression of LC3BII,p-eNOS,eNOS protein and the ratio of LC3BII/LC3BI,p-eNOS/eNOS,and reduce the expression of LC3BI and p62 protein in LSEC,which is statistically significant compared with the model group(P<0.05).Conclusion:Qishen decoction can inhibit the dedifferentiation of LSEC by promoting the autophagy level of LSEC,and then play an anti-fibrosis role.展开更多
Hepatic sinusoidal endothelial cell is a highly differentiated cell in hepatic sinusoid,and plays an important role in the occurrence and development of hepatic fibrosis.The dysfunction of hepatic sinusoidal endotheli...Hepatic sinusoidal endothelial cell is a highly differentiated cell in hepatic sinusoid,and plays an important role in the occurrence and development of hepatic fibrosis.The dysfunction of hepatic sinusoidal endothelial cells is considered to be the key cause of a variety of liver diseases.At present,the researches on hepatic fibrosis at home and abroad are mainly focused on inhibiting the activation of hepatic stellate cells and accelerating the hydrolysis of extracellular matrix.However,there are few studies on the important role of the structure and function of hepatic sinusoidal endothelial cells in hepatic fibrosis.This paper reviews the research progress on the effect of hepatic sinusoidal endothelial cells on hepatic fibrosis and its regulatory mechanism in recent years.This paper summarizes the results of the research on the structural characteristics of hepatic sinusoidal endothelial cells,secretion of fibrosis-related cytokines and regulation of hepatic stellate cells activation in the development of hepatic fibrosis.展开更多
Hepatic sinusoidal endothelial cells are a kind of highly differentiated cells in hepatic sinusoids, which play an important role in the occurrence and development of liver fibrosis. Hepatic sinusoidal endothelial cel...Hepatic sinusoidal endothelial cells are a kind of highly differentiated cells in hepatic sinusoids, which play an important role in the occurrence and development of liver fibrosis. Hepatic sinusoidal endothelial cells are often used in the study of liver fibrosis. In the process of culturing liver sinusoidal endothelial cells, the treatment of serum for culture and cryopreservation of cells are relatively complicated and error-prone. If the technical details of serum treatment and cell cryopreservation are not handled properly, it will have a more obvious effect on the effect of hepatic sinusoidal endothelial cell culture. We have gained experience in the theoretical study of liver fibrosis and the operation of cell culture experiments, and this paper summarized the details of liver sinusoidal endothelial cell culture such as the problems of serum preservation, thawing, precipitates and heat inactivation, as well as methods and precautions for cell cryopreservation.展开更多
<strong>Objective:</strong> Based on the GEO database, the differential genes of sinusoidal endothelial cells in cirrhotic rats were analyzed. <strong>Methods:</strong> In the GEO database, the...<strong>Objective:</strong> Based on the GEO database, the differential genes of sinusoidal endothelial cells in cirrhotic rats were analyzed. <strong>Methods:</strong> In the GEO database, the differential gene expressions of liver sinusoidal endothelial cells in cirrhotic rats were obtained. The screening was performed according to P < 0.01 and differential multiple factor ≥ 4. The obtained genes were input into the DAVID database for enrichment analysis of genes and pathways. The GeneMania and string databases were then used for protein interaction analysis. <strong>Results:</strong> The GSE1843 dataset was obtained in the GEO database, and three pathways significantly associated with cirrhosis and 13 differential genes enriched in three pathways were screened. Text mining revealed that 11 differential genes were directly associated with cirrhosis. The other two were indirectly linked by other genes. The screened genes and known gene formation networks were discovered by the GeneMania tool. <strong>Conclusion:</strong> CDH2 and COL1A1 may be important target genes for cirrhosis.展开更多
Background and aims:Through visual analysis of related literature,the main research direction and hot spots of liver sinusoidal endothelial cells(LSECs)in recent 24 years were explored.Methods:This study used bibliome...Background and aims:Through visual analysis of related literature,the main research direction and hot spots of liver sinusoidal endothelial cells(LSECs)in recent 24 years were explored.Methods:This study used bibliometric analysis with CiteSpace,VOSviewer,Biblioshiny and online analytic tool bibliometric.com to provide a quantitative analysis,hot spot mining,and commentary of articles published in the field of LSECs research.The relevant literature in the Web of Science Core Collection(WOSCC)was searched from 2000 to 2023.The publications with topics or titles or keywords containing LSECs were included into this study.The countries,organizations,journals,authors,and keywords of the publications were summarized and analyzed.Results:This study included 3,747 publications from 14,132 authors belonging to 389 institutions in 61 countries/regions and published in 150 journals,with 156,309 citations.The United States contributed most(1,150)to the publications.The most productive institution was the University of Sydney.Hepatology accounts for the most output(293,7.8%),European authors had a widespread cooperation.The most productive author was Adam DH with 68 papers.Immunological function of LSECs is research hot spot.Conclusion:This study highlights key trends based on a large dataset of the most influential publications about LSECs research over a 24-year period.It provides important clues and ideas for researchers focusing in this area and facilitates future liver disease mechanism,understanding,and treatment.展开更多
AIM： To study the regulatory mechanisms of sinusoida regeneration after partial hepatectomy. METHODS： We invesldgated the expression of angiopoietin （Ang）-1, Ang-2, Tie-2, and vascular endothelial growth factor （...AIM： To study the regulatory mechanisms of sinusoida regeneration after partial hepatectomy. METHODS： We invesldgated the expression of angiopoietin （Ang）-1, Ang-2, Tie-2, and vascular endothelial growth factor （VEGF） in regenerating liver tissue by quantitative reverse-transcription polymerase chain reaction （RT- PCR） using a LightCycler （Roche Diagnostics） and also immunohistochemical staining after 70% hepatectomy in rats. In the next step, we isolated liver cells （hepatocytes, sinusoidal endothelial cell （SEC）, Kupffer cell, and hepatic stellate cells （HSC）） from regenerating liver tissue by in situ collagenase perfusion and counterflow elutriation, to determine potential cellular sources of these angiogenic factors after hepatectomy. Proliferation and apoptosis of SECs were also evaluated by proliferating cell nuclear antigen （PCNA） staining and the terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling （TUNEL） assay, respectively. RESULTS： VEGF mRNA expression increased with a peak at 72 h after hepatectomy, decreasing thereafter. The expression of Ang-1 mRNA was present at detectable levels before hepatectomy and increased slowly with a peak at 96 h. Meanwhile, Ang-2 mRNA was hardly detected before hepatectomy, but was remarkably induced at 120 and 144 h. In isolated cells, VEGF mRNA expression was found mainly in the hepatocyte fraction. Meanwhile, mRNA for Ang-1 and Ang-2 was found in the SEC and HSC fractions, but was more prominent in the latter. The PCNA labeling index of SECs increased slowly, reaching a peak at 72 h, whereas apoptotic SECs were detected between 120 h and 144 h. CONCLUSION： Ang-Tie system, together with VEGF, plays a critical role in regulating balance between SEC proliferation and apoptosis during sinusoidal regeneration after hepatectomy. However, the VEGF system plays a more important role in the early phase of sinusoidal regeneration than angiopoietin/Tie system.展开更多
AIM： To determine whether insulin could promote sinusoidal endothelial cell （SEC） proliferation mediated by upregulation of vascular endothelial growth factor （VEGF） in regenerating rat liver after partial hepate...AIM： To determine whether insulin could promote sinusoidal endothelial cell （SEC） proliferation mediated by upregulation of vascular endothelial growth factor （VEGF） in regenerating rat liver after partial hepatectomy （PHx）. METHODS： Adult male Sprague-Dawley rats undergoing 70% PHx were injected with insulin （300 MU/kg） or saline via the tail veins every 8 h after surgery for 7 d and killed at 0, 24, 48, 72, 96, 120, 144, and 168 h after surgery. Proliferation of both hepatocytes and SECs was monitored by evaluating the proliferating cell nuclear antigen （PCNA） labeling index （LI）. The expression of VEGF protein was evaluated by immunohistochemistJv. The mRNA expressions of VEGF and its receptors FIt-1 and FIk-1 were evaluated by semi-quantitative reverse transcription-PCR. RESULTS： Insulin markedly increased the expression of VEGF mRNA between 24 and 120 h after hepatectomy compared to controls. Similarly, insulin significantly increased the expression of Fit-1 between 24 and 96 h. However, insulin had no significant effect on FIk-1. Furthermore, the immunohistochemical staining revealed that expression of VEGF protein increased in the insulin groups. Insulin significantly increased the PCNA LI of hepatocytes and SECs compared to controls. CONCLUSION： Exogenous insulin may promote SEC proliferation with an enhanced expression of VEGF and its receptor Fit-1 in regenerating rat liver after PHx.展开更多
Liver fibrosis is a necessary stage in the progression of chronic liver disease to cirrhosis.So far,no satisfactory drugs have been found to intervene in liver fibrosis.Liver microcirculation disorders are one of the ...Liver fibrosis is a necessary stage in the progression of chronic liver disease to cirrhosis.So far,no satisfactory drugs have been found to intervene in liver fibrosis.Liver microcirculation disorders are one of the important pathogenesis of chronic liver disease,and hepatic sinusoidal endothelial cells(HSECs)are the main cells that constitute the liver microcirculation barrier.In clinical practice,W-P bodies have been detected in HSECs of most patients with liver fibrosis.W-P bodies serve as a site for the synthesis and storage of vW factors,ET-1 and other cytokines that promote liver fibrosis.They can disrupt the structure and function of HSECs,cause liver microcirculation disorders,and exacerbate the progression of liver fibrosis.Previous studies have found that the Guangxi specialty ethnic medicine,C.kwangsiensis S.G.Lee et C.F.Liang,has definite effects in promoting blood circulation,resolving blood stasis,and resisting liver fibrosis.Based on this,a further research idea has been derived,stating that the blood circulation-promoting,blood stasis-resolving,and anti-liver fibrosis effects of C.kwangsiensis are produced by affecting the formation of W-P bodies,the synthesis and storage of contents in W-P bodies,and intervening in their exocytosis capacity.展开更多
Autophagy is the liver cell energy recycling system regulating a variety of homeostatic mechanisms.Damaged organelles,lipids and proteins are degraded in the lysosomes and their elements are re-used by the cell.Invest...Autophagy is the liver cell energy recycling system regulating a variety of homeostatic mechanisms.Damaged organelles,lipids and proteins are degraded in the lysosomes and their elements are re-used by the cell.Investigations on autophagy have led to the award of two Nobel Prizes and a health of important reports.In this review we describe the fundamental functions of autophagy in the liver including new data on the regulation of autophagy.Moreover we emphasize the fact that autophagy acts like a two edge sword in many occasions with the most prominent paradigm being its involvement in the initiation and progress of hepatocellular carcinoma.We also focused to the implication of autophagy and its specialized forms of lipophagy and mitophagy in the pathogenesis of various liver diseases.We analyzed autophagy not only in well studied diseases,like alcoholic and nonalcoholic fatty liver and liver fibrosis but also in viral hepatitis,biliary diseases,autoimmune hepatitis and rare diseases including inherited metabolic diseases and also acetaminophene hepatotoxicity.We also stressed the different consequences that activation or impairment of autophagy may have in hepatocytes as opposed to Kupffer cells,sinusoidal endothelial cells or hepatic stellate cells.Finally,we analyzed the limited clinical data compared to the extensive experimental evidence and the possible future therapeutic interventions based on autophagy manipulation.展开更多
The onset of alcoholic liver disease (ALD) is initiated by different cell types in the liver and a number of different factors including: products derived from ethanol-induced inflammation, ethanol metabolites, and th...The onset of alcoholic liver disease (ALD) is initiated by different cell types in the liver and a number of different factors including: products derived from ethanol-induced inflammation, ethanol metabolites, and the indirect reactions from those metabolites. Ethanol oxidation results in the production of metabolites that have been shown to bind and form protein adducts, and to increase inflammatory, fibrotic and cirrhotic responses. Lipopolysaccharide (LPS) has many deleterious effects and plays a significant role in a number of disease processes by increasing inflammatory cytokine release. In ALD, LPS is thought to be derived from a breakdown in the intestinal wall enabling LPS from resident gut bacterial cell walls to leak into the blood stream. The ability of adducts and LPS to independently stimulate the various cells of the liver provides for a two-hit mechanism by which various biological responses are induced and result in liver injury. Therefore, the purpose of this article is to evaluate the effects of a two-hit combination of ethanol metabolites and LPS on the cells of the liver to increase inflamma-tion and fi brosis, and play a role in the development and/or progression of ALD.展开更多
Background Proteins or peptides can be directly transferred into cells when covalently linked to protein transduction domains （PTDs）. TAT is one of the most widely studied PTDs. The effect of fusion protein TAT and ...Background Proteins or peptides can be directly transferred into cells when covalently linked to protein transduction domains （PTDs）. TAT is one of the most widely studied PTDs. The effect of fusion protein TAT and heme oxygenase-1 （HO-1） on liver sinusoidal endothelial cells （SECs） apoptosis during cold storage is unknown. The present study aimed to determine whether fusion protein TAT-HO-1 would transduce efficiently into liver during cold storage, and, if so, to determine whether TAT-HO-1 would attenuate SECs apoptosis during preservation injury in rat. Methods Livers of Sprague-Dawley rats were harvested and randomly assigned to group 1 （HTK solution） and group 2 （HTK solution containing TAT-HO-1 fusion protein） according to the type of the preservation solution. The transduction efficiency of TAT-HO-1 was examined and the impairment of SECs was assessed during the period of cold storage followed by 1 hour of reperfusion. Results TAT-HO-1 can transduce efficiently into liver during cold storage. A significantly lower apoptotic index of SECs was observed in group 2, at 6, 12 and 18 hours of cold storage after 1 hour reperfusion, when compared with group 1. TAT-HO-1 reduced HA and ET levels in liver at each time point. Both Bcl-2 and Bax protein were expressed in hepatocytes and SECs at the periphery of the sinusoidal space. Moreover, higher Bcl-2 expression and lower Bax expression were observed in group 2. Conclusions TAT-HO-1 can transduce efficiently into rat livers and shows a protective effect on SECs by attenuating apoptosis during cold ischemia/reperfusion injury. Protein transduction will be a novel therapeutic strategy to reduce the risk of preservation injury in liver transplantation.展开更多
基金Supported by the Fund for Scientific Research-Flanders, No. 1.5.001.04N[F.B.]
文摘Nowadays, liver metastasis remains difficult to cure. When tumor cells escape and arrive in the liver sinusoids, they encounter the local defense mechanism specific to the liver. The sinusoidal cells have been widely described in physiologic conditions and in relation to metastasis during the past 30 years. This paper provides an “overview” of how these cells function in health and in diseases such as
基金supported by grants from the National Key Re-search and Development Program of China(2021YFA1100500 and 2016YFA0102100)。
文摘Liver transplantation is the optimal treatment for patients with end-stage liver disease,metabolic liver diseases,and hepatic malignancies that are not amenable to resection.Hepatic ischemia-reperfusion injury(IRI)is the main problem in liver transplantation and liver resection,leading to parenchymal cell injury and organ dysfunction.The damage of liver sinusoidal endothelial cells(LSECs)is a critical event in IRI.LSECs work as an important regulating factor of liver regeneration after partial hepatectomy.This review primarily describes the mechanisms of LSECs injury in IRI and explores the roles of LSECs in liver regeneration,and briefly introduces the protective strategies targeting LSECs damaged in IRI.
基金Supported by National Natural Science Foundation of China(81960761,82060825)Guangxi Natural Science Foundation(2020GXNSFAA297119)+2 种基金Guangxi First-class Discipline of Traditional Chinese Medicine(GJKY[2022]1)Guangxi Famous TCM Doctor Linjang Inheritance Studio(GZYYKJF[2021]6)Guangxi Postgraduate Education Innovation Program(YCSY2023004,YCSZ2022002).
文摘Hepatic stellate cells,hepatic sinusoidal endothelial cells and hepatic sinusoidal capllarization are closely related to the occurrence and progression of hepatic fibrosis.The pathological activation of hepatic stellate cels is the central link of hepatic fibrosis,and hepatic sinusoidal capillarization also promotes the occurrence and development of liver diseases.In the course of hepatic fibrosis,there is always a mutually reinforcing relationship between the activation of hepatic stellate cells and the capillarization of hepatic sinusoids.This paper strives to find an effective way to intervene or even reverse this vicious cycle by deeply investigating the effect of hepatic stellate cells and hepatic sinusoidal capillarization on hepatic fibrosis and their mutual promotion,and provide a new idea for the treatment of hepatic fibrosis,which is of great significance for relieving and reversing hepatic fibrosis.
基金Supported by the Young Elite Scientists Sponsorship Program by CAST,No.2016QNRC001Beijing Natural Science Foundation,No.7172187
文摘Cirrhosis develops from liver fibrosis and is the severe pathological stage of all chronic liver injury. Cirrhosis caused by hepatitis B virus and hepatitis C virus infection is especially common. Liver fibrosis and cirrhosis involve excess production of extracellular matrix,which is closely related to liver sinusoidal endothelial cells(LSECs). Damaged LSECs can synthesize transforming growth factor-beta and platelet-derived growth factor,which activate hepatic stellate cells and facilitate the synthesis of extracellular matrix. Herein,we highlight the angiogenic cytokines of LSECs related to liver fibrosis and cirrhosis at different stages and focus on the formation and development of liver fibrosis and cirrhosis. Inhibition of LSEC angiogenesis and antiangiogenic therapy are described in detail. Targeting LSECs has high therapeutic potential for liver diseases. Further understanding of the mechanism of action will provide stronger evidence for the development of anti-LSEC drugs and new directions for diagnosis and treatment of liver diseases.
文摘Important advances have been made in research into the mechanism of alcoholic liver disease (ALD) over the past few years,but the role of liver sinusoidal endothelial cell (LSEC) in ALD has not been elucidated adequately. This study was undertaken to investigate the effect of ethanol on fenestrae of LSECs in rats. METHODS: A rat model of alcoholic liver disease was established by means of direct intragastric instillation of ethanol. Fifty-five rats of experimental (35 rats) and control (20) groups were sacrificed at the end of 4,8,12 weeks respectively, and also at the end of 12-week abstinence. After heart perfusion, the liver tissue was fixed and stained with hematoxylin and eosin for observation of serial changes of LSEC-fenestrae under a transmission electron microscope. RESULTS: Normal LESC was flat with a nucleus and organelles arranged regularly. The distal cytoplasm displayed as a lamina with many fenestrae, lacking the basement membrane(BM) underneath the endothelium. At the end of 4-week alcohol feeding, the number of fenestrae decreased at the distal cytoplasm in some LSECs, without the formation of the BM underneath the endothelium. At the end of 8 weeks, the number of fenestrae decreased significantly or even disappeared. The BM began to develop incompletely underneath the endothelium, while the active fibroblast appeared. At the end of 12 weeks, the number of fenestrae decreased more significantly and the complete BM could even be seen. But the changes were mostly limited in the single or adjoining sinus, and fibrosis was scarcely formed. At the end of 12-week abstinence, defenestration and formation of the endothelial BM lightened significantly. CONCLUSIONS:Defenestration and formation of the BM in LSECs develop gradually with the chronic stimulation of ethanol. Hepatic sinusoidal capillarization and fibrosis will be seen if their state is more serious. These early changes, i. e., limited and regional defenestration and capillarization may be the basis of alcoholic peri-fibrosis. This kind of he- patic fibrosis is reversible after removal of etiological factors.
文摘OBJECTIVE To investigate the effect of co-culture between colon cancer cells （SW1116） and human liver sinusoidal endothelial cells （HLSECs） on cancer cell metastasis, and to provide a novel model for studying the mechanism of colon cancer liver metastasis. METHODS HLSECs and SW1116 were co-cultured for 21 rounds in vitro. Transwell migration, gelatin-zymography, CCK-8 proliferation and colony formation assays were used to examine the invasion, proliferation, and colony forming ability of cancer cells. Assays were carried out to examine tumor growth ability and liver metastasis. The associated molecular change was examined by western blotting. RESULTS After 21 selection rounds, colon cancer cells SWl 1161）21 displayed a clear boundary. Compared with the 5W1116 cells, SW1116P21 cells had a greater invasive ability, cell proliferation and colony formation in soft agar. A gelatin-zymography assay showed that the ability of SW1116P21 cells to secrete matrix metalloproteinase-2/9 was significantly greater than that of SWl116 cells. Additionally, the capacity for subcutaneous tumor formation of SW1116P21 was significantly increased. It was found that mice injected with SW1116P21 cells developed significantly more visually observable liver nodules than mice injected with SW1116 cells. Western blotting showed increased vimentin expression and decreased E-cadherin expression in the SW1116P21 cells, compared with the SWl 116 cells. CONCLUSION The interaction between SW1116 and HLSECs may promote tumor cell invasion, proliferation and colony formation in vitro, and tumor formation and liver metastasis in vivo. An epithelial-mesenchymal transition occurs in SWl 116P21 cells, which contributes to the change in the characteristics of tumor cells.
基金Supported by JSPS KAKENHI Grant,No.JP17K10503(to Matsuno N)and JP20K11539(to Bochimoto H).
文摘BACKGROUND The machine perfusion(MP)preservation including hypothermic MP(HMP)and midthermic MP(MMP)has been considered as a promising strategy to preserve the functions of liver donated after cardiac death.The importance of understanding liver sinusoidal endothelial cells(LSEC)damage in regulating liver injury during MP has been emphasized.However,the ultrastructural changes in the LSEC and sinusoids around them after MP are unclear.AIM To investigate the ultrastructural changes in the LSEC and sinusoids around them after MP.METHODS Porcine liver grafts undergo a warm ischemia time of 60 minutes perfused for 4 h with modified University of Wisconsin gluconate solution.Group A grafts were preserved with HMP at 8℃ constantly for 4 h.Group B grafts were preserved with a rewarming solution at 22℃ by MMP for 4 h.Then the ultrastructural changes in the LSEC and sinusoids in Group A and B were comparatively analyzed by using osmium-maceration scanning electron microscopy with complementary transmission electron microscopy methods.RESULTS An analysis of the LSEC after warm ischemia revealed that mitochondria with condensed-shaped cristae,abnormal vesicles,reduction of ribosomes and the endoplasmic reticulum(ER)surround the mitochondria appeared.The MP subsequent after warm ischemia alleviate the abnormal vesicles and reduction of ribosomes in LSEC,which indicated the reduction of the ER damage.However,MMP could restore the tubular mitochondrial cristae,while after HMP the condensed and narrow mitochondrial cristae remained.In addition,the volume of the sinusoidal space in the liver grafts after MMP were restored,which indicated a lower risk of pressure injury than HMP.CONCLUSION MMP alleviates the ER damage of LSEC by warm ischemia,additionally restore the metabolism of LSEC via the normalization of mitochondria and prevent the share stress damage of liver grafts.
基金National Natural Science Foundation of China(No.81760151)。
文摘Hepatic sinusoidal endothelial cell(LSECs),as the sinusoidal capillary channel of the liver,is the most abundant non-parenchymal cell group in the liver. LSECs not only forms a barrier in the hepatic sinusoid,but also has important physiological and immunological functions,including filtration,endocytosis,antigen presentation and leukocyte recruitment. It has been clear that LSECs play an important role in maintaining immune homeostasis in the liver and delaying the immune response to acute and chronic liver injury. In this review,we summarize how LSECs affect the immune microenvironment in the liver,and discuss their role in immune-mediated chronic liver disease,carcinogenesis,inflammation and aging process.
基金Heilongjiang Traditional Chinese Medicine Research Project(No.ZHY18-029, ZHY19-061, ZHY19-062)Heilongjiang Natural Science FoundationJoint Guiding Project(No.LH2019H095)National Administration of TraditionalChinese Medicine(No.2016ZX05)
文摘Objective:To observe the effect of Qishen decoction on dedifferentiation and autophagy of liver sinusoid endothelial cells(LSEC);Methods:LSEC were randomly divided into the control group,model group,Qishen Decoction low,medium,high dose group,and inhibitor group.The model was induced by 100μg/ml oxidized low-density lipoprotein(oxLDL)for 24 hours,and the corresponding drugs or medicated serum were given for intervention.The expression levels of VEGFR2 and ET1 were detected by RT-qPCR and immunofluorescence staining,the ultrastructure of LSEC was detected by transmission electron microscopy,the content of NO was detected by ELISA,the expression levels of autophagy related proteins(LC3BI,LC3BⅡand p62)and endothelial function related proteins(eNOS and p-eNOS)were detected by western blot;Results:The results of transmission electron microscopy showed that Qishen decoction medicated serum could increase the number of fenestra and autophagy in LSEC cells,and inhibit the formation of basement membrane under endothelium.Compared with the model group,Qishen decoction medicated serum could significantly up-regulate the expression level of VEGFR2 mRNA and protein in LSEC,down regulate the expression level of ET1 mRNA and protein,the difference was statistically significant(P<0.05).In addition,Qishen decoction medicated serum could significantly increase the expression of LC3BII,p-eNOS,eNOS protein and the ratio of LC3BII/LC3BI,p-eNOS/eNOS,and reduce the expression of LC3BI and p62 protein in LSEC,which is statistically significant compared with the model group(P<0.05).Conclusion:Qishen decoction can inhibit the dedifferentiation of LSEC by promoting the autophagy level of LSEC,and then play an anti-fibrosis role.
基金National Natural Science Foundation of China(81960761,81960751,81902764).
文摘Hepatic sinusoidal endothelial cell is a highly differentiated cell in hepatic sinusoid,and plays an important role in the occurrence and development of hepatic fibrosis.The dysfunction of hepatic sinusoidal endothelial cells is considered to be the key cause of a variety of liver diseases.At present,the researches on hepatic fibrosis at home and abroad are mainly focused on inhibiting the activation of hepatic stellate cells and accelerating the hydrolysis of extracellular matrix.However,there are few studies on the important role of the structure and function of hepatic sinusoidal endothelial cells in hepatic fibrosis.This paper reviews the research progress on the effect of hepatic sinusoidal endothelial cells on hepatic fibrosis and its regulatory mechanism in recent years.This paper summarizes the results of the research on the structural characteristics of hepatic sinusoidal endothelial cells,secretion of fibrosis-related cytokines and regulation of hepatic stellate cells activation in the development of hepatic fibrosis.
基金Supported by National Nature Science Foundation of China(8196076181960751,81902764)Guangxi Natural Science Foundation(2020JJA140257)The Training Project for Excellent Middle-aged/Young Teachers in Guangx Higher Education Institutions(2018KY1149)。
文摘Hepatic sinusoidal endothelial cells are a kind of highly differentiated cells in hepatic sinusoids, which play an important role in the occurrence and development of liver fibrosis. Hepatic sinusoidal endothelial cells are often used in the study of liver fibrosis. In the process of culturing liver sinusoidal endothelial cells, the treatment of serum for culture and cryopreservation of cells are relatively complicated and error-prone. If the technical details of serum treatment and cell cryopreservation are not handled properly, it will have a more obvious effect on the effect of hepatic sinusoidal endothelial cell culture. We have gained experience in the theoretical study of liver fibrosis and the operation of cell culture experiments, and this paper summarized the details of liver sinusoidal endothelial cell culture such as the problems of serum preservation, thawing, precipitates and heat inactivation, as well as methods and precautions for cell cryopreservation.
文摘<strong>Objective:</strong> Based on the GEO database, the differential genes of sinusoidal endothelial cells in cirrhotic rats were analyzed. <strong>Methods:</strong> In the GEO database, the differential gene expressions of liver sinusoidal endothelial cells in cirrhotic rats were obtained. The screening was performed according to P < 0.01 and differential multiple factor ≥ 4. The obtained genes were input into the DAVID database for enrichment analysis of genes and pathways. The GeneMania and string databases were then used for protein interaction analysis. <strong>Results:</strong> The GSE1843 dataset was obtained in the GEO database, and three pathways significantly associated with cirrhosis and 13 differential genes enriched in three pathways were screened. Text mining revealed that 11 differential genes were directly associated with cirrhosis. The other two were indirectly linked by other genes. The screened genes and known gene formation networks were discovered by the GeneMania tool. <strong>Conclusion:</strong> CDH2 and COL1A1 may be important target genes for cirrhosis.
基金supported in part by the Institute of Bioengineering&Bioimaging,Biomedical Research Council,Agency for Science,Technology and Research(A*STAR),A*STAR(Project#A20D3b0073)Good Food Institute Research Program+3 种基金IAF(H18/01/a0/017)SMART CAMP,The Institute for Digital Medicine(WisDM),Mechanobiology Institute of Singapore(A-0003467-22-00)funding to HYU.This work is also supported by Capital's Funds for Health Improvement and Research(2022-2Z-20113)National Science and Technology Major Project(No.2017ZX09101001-002-044)Xuanwu Hospital of Capital Medical University“Huizhi”talent engineering scholars program-Training program.
文摘Background and aims:Through visual analysis of related literature,the main research direction and hot spots of liver sinusoidal endothelial cells(LSECs)in recent 24 years were explored.Methods:This study used bibliometric analysis with CiteSpace,VOSviewer,Biblioshiny and online analytic tool bibliometric.com to provide a quantitative analysis,hot spot mining,and commentary of articles published in the field of LSECs research.The relevant literature in the Web of Science Core Collection(WOSCC)was searched from 2000 to 2023.The publications with topics or titles or keywords containing LSECs were included into this study.The countries,organizations,journals,authors,and keywords of the publications were summarized and analyzed.Results:This study included 3,747 publications from 14,132 authors belonging to 389 institutions in 61 countries/regions and published in 150 journals,with 156,309 citations.The United States contributed most(1,150)to the publications.The most productive institution was the University of Sydney.Hepatology accounts for the most output(293,7.8%),European authors had a widespread cooperation.The most productive author was Adam DH with 68 papers.Immunological function of LSECs is research hot spot.Conclusion:This study highlights key trends based on a large dataset of the most influential publications about LSECs research over a 24-year period.It provides important clues and ideas for researchers focusing in this area and facilitates future liver disease mechanism,understanding,and treatment.
文摘AIM： To study the regulatory mechanisms of sinusoida regeneration after partial hepatectomy. METHODS： We invesldgated the expression of angiopoietin （Ang）-1, Ang-2, Tie-2, and vascular endothelial growth factor （VEGF） in regenerating liver tissue by quantitative reverse-transcription polymerase chain reaction （RT- PCR） using a LightCycler （Roche Diagnostics） and also immunohistochemical staining after 70% hepatectomy in rats. In the next step, we isolated liver cells （hepatocytes, sinusoidal endothelial cell （SEC）, Kupffer cell, and hepatic stellate cells （HSC）） from regenerating liver tissue by in situ collagenase perfusion and counterflow elutriation, to determine potential cellular sources of these angiogenic factors after hepatectomy. Proliferation and apoptosis of SECs were also evaluated by proliferating cell nuclear antigen （PCNA） staining and the terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling （TUNEL） assay, respectively. RESULTS： VEGF mRNA expression increased with a peak at 72 h after hepatectomy, decreasing thereafter. The expression of Ang-1 mRNA was present at detectable levels before hepatectomy and increased slowly with a peak at 96 h. Meanwhile, Ang-2 mRNA was hardly detected before hepatectomy, but was remarkably induced at 120 and 144 h. In isolated cells, VEGF mRNA expression was found mainly in the hepatocyte fraction. Meanwhile, mRNA for Ang-1 and Ang-2 was found in the SEC and HSC fractions, but was more prominent in the latter. The PCNA labeling index of SECs increased slowly, reaching a peak at 72 h, whereas apoptotic SECs were detected between 120 h and 144 h. CONCLUSION： Ang-Tie system, together with VEGF, plays a critical role in regulating balance between SEC proliferation and apoptosis during sinusoidal regeneration after hepatectomy. However, the VEGF system plays a more important role in the early phase of sinusoidal regeneration than angiopoietin/Tie system.
文摘AIM： To determine whether insulin could promote sinusoidal endothelial cell （SEC） proliferation mediated by upregulation of vascular endothelial growth factor （VEGF） in regenerating rat liver after partial hepatectomy （PHx）. METHODS： Adult male Sprague-Dawley rats undergoing 70% PHx were injected with insulin （300 MU/kg） or saline via the tail veins every 8 h after surgery for 7 d and killed at 0, 24, 48, 72, 96, 120, 144, and 168 h after surgery. Proliferation of both hepatocytes and SECs was monitored by evaluating the proliferating cell nuclear antigen （PCNA） labeling index （LI）. The expression of VEGF protein was evaluated by immunohistochemistJv. The mRNA expressions of VEGF and its receptors FIt-1 and FIk-1 were evaluated by semi-quantitative reverse transcription-PCR. RESULTS： Insulin markedly increased the expression of VEGF mRNA between 24 and 120 h after hepatectomy compared to controls. Similarly, insulin significantly increased the expression of Fit-1 between 24 and 96 h. However, insulin had no significant effect on FIk-1. Furthermore, the immunohistochemical staining revealed that expression of VEGF protein increased in the insulin groups. Insulin significantly increased the PCNA LI of hepatocytes and SECs compared to controls. CONCLUSION： Exogenous insulin may promote SEC proliferation with an enhanced expression of VEGF and its receptor Fit-1 in regenerating rat liver after PHx.
基金Supported by National Natural Science Foundation of China(81960761,82060825)Natural Science Foundation of Guangxi(2020GXNSFAA297119)+2 种基金First-class Discipline in Guangxi:Traditional Chinese Medicine(GJKY[2022]1)Guangxi Famous Traditional Chinese Medicine Doctor Linjiang Inheritance Studio(GZYYKJF[2021]6)Guangxi Graduate Education Innovation Program(YCSY2023004,YCSZ2022002).
文摘Liver fibrosis is a necessary stage in the progression of chronic liver disease to cirrhosis.So far,no satisfactory drugs have been found to intervene in liver fibrosis.Liver microcirculation disorders are one of the important pathogenesis of chronic liver disease,and hepatic sinusoidal endothelial cells(HSECs)are the main cells that constitute the liver microcirculation barrier.In clinical practice,W-P bodies have been detected in HSECs of most patients with liver fibrosis.W-P bodies serve as a site for the synthesis and storage of vW factors,ET-1 and other cytokines that promote liver fibrosis.They can disrupt the structure and function of HSECs,cause liver microcirculation disorders,and exacerbate the progression of liver fibrosis.Previous studies have found that the Guangxi specialty ethnic medicine,C.kwangsiensis S.G.Lee et C.F.Liang,has definite effects in promoting blood circulation,resolving blood stasis,and resisting liver fibrosis.Based on this,a further research idea has been derived,stating that the blood circulation-promoting,blood stasis-resolving,and anti-liver fibrosis effects of C.kwangsiensis are produced by affecting the formation of W-P bodies,the synthesis and storage of contents in W-P bodies,and intervening in their exocytosis capacity.
文摘Autophagy is the liver cell energy recycling system regulating a variety of homeostatic mechanisms.Damaged organelles,lipids and proteins are degraded in the lysosomes and their elements are re-used by the cell.Investigations on autophagy have led to the award of two Nobel Prizes and a health of important reports.In this review we describe the fundamental functions of autophagy in the liver including new data on the regulation of autophagy.Moreover we emphasize the fact that autophagy acts like a two edge sword in many occasions with the most prominent paradigm being its involvement in the initiation and progress of hepatocellular carcinoma.We also focused to the implication of autophagy and its specialized forms of lipophagy and mitophagy in the pathogenesis of various liver diseases.We analyzed autophagy not only in well studied diseases,like alcoholic and nonalcoholic fatty liver and liver fibrosis but also in viral hepatitis,biliary diseases,autoimmune hepatitis and rare diseases including inherited metabolic diseases and also acetaminophene hepatotoxicity.We also stressed the different consequences that activation or impairment of autophagy may have in hepatocytes as opposed to Kupffer cells,sinusoidal endothelial cells or hepatic stellate cells.Finally,we analyzed the limited clinical data compared to the extensive experimental evidence and the possible future therapeutic interventions based on autophagy manipulation.
文摘The onset of alcoholic liver disease (ALD) is initiated by different cell types in the liver and a number of different factors including: products derived from ethanol-induced inflammation, ethanol metabolites, and the indirect reactions from those metabolites. Ethanol oxidation results in the production of metabolites that have been shown to bind and form protein adducts, and to increase inflammatory, fibrotic and cirrhotic responses. Lipopolysaccharide (LPS) has many deleterious effects and plays a significant role in a number of disease processes by increasing inflammatory cytokine release. In ALD, LPS is thought to be derived from a breakdown in the intestinal wall enabling LPS from resident gut bacterial cell walls to leak into the blood stream. The ability of adducts and LPS to independently stimulate the various cells of the liver provides for a two-hit mechanism by which various biological responses are induced and result in liver injury. Therefore, the purpose of this article is to evaluate the effects of a two-hit combination of ethanol metabolites and LPS on the cells of the liver to increase inflamma-tion and fi brosis, and play a role in the development and/or progression of ALD.
基金This study was supported by a grant from National Natural Science Foundation of China （No. 30672024）.
文摘Background Proteins or peptides can be directly transferred into cells when covalently linked to protein transduction domains （PTDs）. TAT is one of the most widely studied PTDs. The effect of fusion protein TAT and heme oxygenase-1 （HO-1） on liver sinusoidal endothelial cells （SECs） apoptosis during cold storage is unknown. The present study aimed to determine whether fusion protein TAT-HO-1 would transduce efficiently into liver during cold storage, and, if so, to determine whether TAT-HO-1 would attenuate SECs apoptosis during preservation injury in rat. Methods Livers of Sprague-Dawley rats were harvested and randomly assigned to group 1 （HTK solution） and group 2 （HTK solution containing TAT-HO-1 fusion protein） according to the type of the preservation solution. The transduction efficiency of TAT-HO-1 was examined and the impairment of SECs was assessed during the period of cold storage followed by 1 hour of reperfusion. Results TAT-HO-1 can transduce efficiently into liver during cold storage. A significantly lower apoptotic index of SECs was observed in group 2, at 6, 12 and 18 hours of cold storage after 1 hour reperfusion, when compared with group 1. TAT-HO-1 reduced HA and ET levels in liver at each time point. Both Bcl-2 and Bax protein were expressed in hepatocytes and SECs at the periphery of the sinusoidal space. Moreover, higher Bcl-2 expression and lower Bax expression were observed in group 2. Conclusions TAT-HO-1 can transduce efficiently into rat livers and shows a protective effect on SECs by attenuating apoptosis during cold ischemia/reperfusion injury. Protein transduction will be a novel therapeutic strategy to reduce the risk of preservation injury in liver transplantation.
