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Preparation and in vitro studies of microencapsulated cells releasing human tissue inhibitor of metalloproteinase-2 被引量:2
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作者 姜强 张苏展 +1 位作者 彭佳萍 王旭林 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2005年第9期859-864,共6页
Objective: To prepare microencapsulated cells releasing human tissue inhibitor ofmetalloproteinase-2 (TIMP-2), and investigate their biological characteristics in vitro. Methods: Chinese hamster ovary (CHO) cell... Objective: To prepare microencapsulated cells releasing human tissue inhibitor ofmetalloproteinase-2 (TIMP-2), and investigate their biological characteristics in vitro. Methods: Chinese hamster ovary (CHO) cells were stably transfected with a human TIMP-2 expression vector, encapsulated in barium alginate microcapsules and cultured in vitro. Morphological appearance of the microcapsules was observed under a light microscope. Cell viability was assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Enzyme linked immunosorbent assay (ELISA) and reverse zymography were used to confirm the release of biologically active TIMP-2 from the microcapsules. Cryopreservation study of the microencapsulated cells was carried out using dimethyl sulfoxide (DMSO) as preservative agent. Results: The microcapsules appeared like a sphere with diameter of 300-600 ~tm. The surface of the capsule wall was clearly smooth. The microencapsulated cells survived well and kept proliferating over the 6 weeks observed. No significant difference in TIMP-2 secretion was found between encapsulated and unencapsulated cells. Reverse zymography confirmed the bioactivity of MMP (matrix metalloproteinase) inhibition of TIMP-2. The cryopreservation process did not damage the microcapsule morphology nor the viability of the cells inside. Conclusion: Microencapsulated engineered CHO cells survive at least 6 weeks after preparation in vitro, and secrete bioactive TIMP-2 freely from the microcapsules. 展开更多
关键词 MICROENCAPSULATION Recombinant cells Human tissue inhibitor of metalloproteinase-2 Cell culture
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Long noncoding RNAs HAND2-AS1 ultrasound microbubbles suppress hepatocellular carcinoma progression by regulating the miR-873-5p/tissue inhibitor of matrix metalloproteinase-2 axis
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作者 Qiang Zou Hao-Wen Wang +2 位作者 Xi-Liang Di Yuan Li Hui Gao 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第4期1547-1563,共17页
BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found t... BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression. 展开更多
关键词 Hepatocellular carcinoma Ultrasound microbubbles Long noncoding RNA HAND2-AS1 miR-873-5p tissue inhibitor of matrix metalloproteinase-2
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Tissue inhibitor of metalloproteinase-3 expression affects clinicopathological features and prognosis of aflatoxin B1-related hepatocellular carcinoma
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作者 Qiu-Ju Liang Qin-Qin Long +3 位作者 Feng-Qin Tian Qun-Ying Su Xiao-Ying Zhu Xi-Dai Long 《World Journal of Hepatology》 2024年第8期1131-1144,共14页
BACKGROUND The dysregulation of tissue inhibitor of metalloproteinase-3(TIMP3)was positively correlated with the progression of hepatocellular carcinoma(HCC).However,it is not clear whether TIMP3 expression is associa... BACKGROUND The dysregulation of tissue inhibitor of metalloproteinase-3(TIMP3)was positively correlated with the progression of hepatocellular carcinoma(HCC).However,it is not clear whether TIMP3 expression is associated with the clinico-pathological features and prognosis of aflatoxin B1(AFB1)-related HCC(AHCC).A retrospective study,including 182 patients with AHCC,was conducted to explore the link between TIMP3 expression in cancerous tissues and the clinico-pathological characteristics and prognosis of AHCC.TIMP3 expression was detected by immunohistochemistry and its effects on the clinicopathological features and prognosis of AHCC were evaluated by Kaplan-Meier survival analysis and Cox regression survival analysis.Odds ratio,hazard ratio(HR),median overall survival time(MST),median tumor recurrence-free survival time(MRT),and corresponding 95%confidential interval(CI)was calculated to RESULTS Kaplan-Meier survival analysis showed that compared with high TIMP3 expression,low TIMP3 expression in tumor tissues significantly decreased the MST(36.00 mo vs 18.00 mo)and MRT(32.00 mo vs 16 mo)of patients with AHCC.Multivariate Cox regression survival analysis further proved that decreased expression of TIMP3 increased the risk of death(HR=2.85,95%CI:2.04-4.00)and tumor recurrence(HR=2.26,95%CI:1.57-3.26).Furthermore,decreased expression of TIMP3 protein in tissues with AHCC was significantly correlated with tumor clinicopatho-logical features,such as tumor size,tumor grade and stage,tumor microvessel density,and tumor blood invasion.Additionally,TIMP3 protein expression was also negatively associated with amount of AFB1-DNA adducts in tumor tissues.CONCLUSION These findings indicate that the dysregulation of TIMP3 expression is related to AHCC biological behaviors and affects tumor outcome,suggesting that TIMP3 may act as a prognostic biomarker for AHCC. 展开更多
关键词 tissue inhibitor of metalloproteinase-3 expression Aflatoxin B1 Hepatocellular carcinoma Clinicopathological feature PROGNOSIS
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Prognostic value of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in bladder carcinoma 被引量:1
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作者 许克新 侯树坤 杜志军 《Chinese Medical Journal》 SCIE CAS CSCD 2002年第5期743-745,155,共3页
OBJECTIVES: To detect the level of matrix metalloproteinase-2 (MMP-2) mRNA and the tissue inhibitor of metalloproteinase-2 (TIMP-2) mRNA in bladder transitional cell carcinoma (BTCC), and to estimate the prognosis for... OBJECTIVES: To detect the level of matrix metalloproteinase-2 (MMP-2) mRNA and the tissue inhibitor of metalloproteinase-2 (TIMP-2) mRNA in bladder transitional cell carcinoma (BTCC), and to estimate the prognosis for bladder tumor based on the quality and quantity of MMP-2 and TIMP-2 mRNA. METHODS: Thirty-five samples of human BTCC and 15 normal fresh bladder tissues were studied by RT-PCR analysis followed by computer-assisted image analysis. RESULTS: The level of the MMP-2 mRNA in BTCC was significantly increased compared with that in normal bladder epithelium. The positive rates of MMP-2 and TIMP-2 mRNA were 71.4% and 65.7% in BTCC, and 66.7% and 60.0% in the normal bladder wall. The expression intensity of the MMP-2 mRNA by image analysis tended to increase with tumor grading and staging, which showed statistical significance. Similarly, the MMP-2 to TIMP-2 ratio also showed statistically significant difference between normal bladder tissue and bladder carcinoma (P 展开更多
关键词 ADULT Aged Aged 80 and over BLADDER Bladder Neoplasms FEMALE Gelatinase A Gene Expression Regulation Neoplastic Humans Male Middle Aged Neoplasm Staging Predictive Value of Tests Prognosis RNA Messenger Research Support Non-U.S. Gov't tissue inhibitor of metalloproteinase-2
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Effects of benazepril on renal function and kidney expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in diabetic rats 被引量:24
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作者 SUN Shu-zhen WANG Yi LI Qian TIAN Yong-jie LIU Ming-hua YU Yong-hui 《Chinese Medical Journal》 SCIE CAS CSCD 2006年第10期814-821,共8页
Background Excessive deposition of extraceUular matrix (ECM) in the kidney is the hallmark of diabetic nephropathy. Increased matrix synthesis has been well documented but the effects of diabetes on degradative path... Background Excessive deposition of extraceUular matrix (ECM) in the kidney is the hallmark of diabetic nephropathy. Increased matrix synthesis has been well documented but the effects of diabetes on degradative pathways, particularly in the in vivo setting. The renal protective effect of these pathways on matrix accumulation has not been fully elucidated. The present study was understaken to investigate the activity of matrix metalloproteinase-2 (MMP-2), the expression of MMP-2 and tissue inhibitor of metalloproteinase-2 (TIMP-2) in kidney tissues of diabetic rats, and to explore the degradative pathway of type Ⅳ collagen (Ⅳ-C) and the renal protective effects of ACE inhibition- benazepril. 展开更多
关键词 angiotensin converting enzyme inhibitors diabetic nephropathy renal function matrix metalloproteinase-2 tissue inhibitor of metalloproteinase-2
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Correlations between papillary thyroid cancer and peripheral blood levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 被引量:8
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作者 ZHOU Shao-fei HU San-yuan +2 位作者 MA Lei MIAO Lei MAO Wei-zheng 《Chinese Medical Journal》 SCIE CAS CSCD 2013年第10期1925-1929,共5页
Background The relationship between the presence of metalloproteinases and thyroid cancer remains unknown, and many controversies still exist in this field. The objective of this study was to investigate the correlati... Background The relationship between the presence of metalloproteinases and thyroid cancer remains unknown, and many controversies still exist in this field. The objective of this study was to investigate the correlations between papillary thyroid cancer and peripheral blood levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metall0Proteinase-2. Methods The correlations were studied bY detecting the levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloProteinase-1, and tissue inhibitor of metalloproteinase-2 by enzyme-linked immunosorbant assay and reverse-transcription polymerase chain reaction in the peripheral blood of 30 patients with papillary thyroid carcinoma, 27 patients with benign thyroid disease, and 25 hea !hy vo!unteers. Results The leve!s of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 in the peripheral blood of patients with papillary thyroid carcinoma were significantly higher than those in the peripheral blood of patients with benign thyroid disease and healthy volunteers (P 〈0.05). However, there were no significant differences between patients with benign thyroid disease and healthy volunteers (P 〉0.05). The accuracy of detection by both enzyme-linked immunosorbant assay and reverse-transcription polymerase chain reaction in the papillary thyroid cancer group was 83.33%. Conclusions The levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 in the peripheral blood are helpful in identifying thyroid carcinoma and aid in preoperative assessment. 展开更多
关键词 thyroid carcinoma matrix metalloproteinase-2 matrix metalloproteinase-9 tissue inhibitor of metalloproteinase-1 tissue inhibitor of metalloproteinase-2
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Cloning and expressing a recombinant human tissue inhibitor of metalloproteinase-2(TIMP-2)in methylotrophic yeast Pichia pastoris and its characterizations
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作者 YAN Xunyou ZHAO Hongliang +2 位作者 ZHANG Weiguang XUE Chong LIU Zhimin 《Frontiers in Biology》 CSCD 2007年第2期170-175,共6页
To obtain human tissue inhibitor of metalloproteinase-2(TIMP-2)cDNA and the secretory expression of TIMP-2 gene in Pichia pastoris,we designed and synthesized a 618 base pairs artificial gene coding for the TIMP-2 wit... To obtain human tissue inhibitor of metalloproteinase-2(TIMP-2)cDNA and the secretory expression of TIMP-2 gene in Pichia pastoris,we designed and synthesized a 618 base pairs artificial gene coding for the TIMP-2 with a computer-aided design method using a standard chemical synthesis technique,which was composed of frequently used codons in the highly expressed Pichia pastoris genes.Then the synthetic gene encoding TIMP-2 was checked by means of dideoxynucleotide sequencing.The verified gene of TIMP2 was cloned to the Escherichia coli-yeast shuttle vector of pPIC9 to construct a recombinant plasmid pPIC9-T2.The plasmid was transformed into GS115 cells of the methylotrophic yeast,Pichia pastoris by electroporation,and we got the expression cell through phenotype selection and induction with methanol.Separation,purification,and bioactivity analysis of the expressed products were performed. 展开更多
关键词 tissue inhibitor of metalloproteinase-2 Pichia pastoris expression bioactivity
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Effects of irbesartan on the expression of matrix metalloproteinase-2/ tissue inhibitor of metalloproteinase-2 in streptozotocin-induced diabetic rat kidney 被引量:7
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作者 LIUBi-cheng XUYan MAKun-ling HUANGHai-quan YINLian-fang LIUDian-ge 《Chinese Medical Journal》 SCIE CAS CSCD 2005年第12期1040-1044,共5页
Glomerular hypertrophy and progressive expansion of extracelluar matrix (ECM) have been regarded as the early feature of diabetic nephropathy (DN), which leads to accumulation of ECM and thickening of glomerular basem... Glomerular hypertrophy and progressive expansion of extracelluar matrix (ECM) have been regarded as the early feature of diabetic nephropathy (DN), which leads to accumulation of ECM and thickening of glomerular basement membrane, and subsequently induces renal fibrosis. Both increasing synthesis and decreasing degradation of matrix components are responsible for matrix accumulation. The later may play more important role in DN that involves a number of matrix metalloproteinases (MMPs). MMPs are a family of proteolytic enzymes whose activity is tightly regulated by tissue inhibitor of metalloproteinases (TIMPs), and the MMP/TIMP ratio is critical for coordinating matrix production and degradation. 1 Recently, considerable evidence suggests that the intrarenal renin-angiotensin system plays an important role in the development of DN. 2 Blockade of the renin-angiotensin system (RAS) by angiotensin-coverting enzyme inhibitor (ACEI) or angiotensin Ⅱ receptor antagonist (AIIRA) delays the progression of renal injury associated with diabetes. 3 AIIRA has been regarded as the first line choice for DN therapy. However, the potential mechanism for AIIRA in the ECM degradative pathway has not been fully elucidated. The present study is to investigate the effect of Irbesartan (Irb), a newly developed AIIRA, on renal expression of MMP-2 and TIMP-2 in streptozotocin (STZ)-induced diabetic rats. 展开更多
关键词 IRBESARTAN diabetic nephropathy matrix metalloproteinase-2 tissue inhibitor of metalloproteinase-2
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Expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic stellate cells during rat hepatic fibrosis and its intervention by IL-10 被引量:35
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作者 Wei-DaZheng Li-JuanZhang Mei-NaShi Zhi-XinChen Yun-XinChen Yue-HongHuang Xiao-ZhongWang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第12期1753-1758,共6页
AIM: To investigate the expression of matrix metallopr-oteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic fibrosis and the antifibrogenic role of exogenous interleukin-10 (IL-10). METHODS: Hepatic fibro... AIM: To investigate the expression of matrix metallopr-oteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic fibrosis and the antifibrogenic role of exogenous interleukin-10 (IL-10). METHODS: Hepatic fibrosis was induced by CCI4 administration and 60 male Sprague-Dawley rats were randomly divided into normal control group (group N, 8 rats), CCI4-induced group (group C, 28 rats) and IL-10-treated group (group I, 24 rats). At the beginning of the 7th and 11th wk, rats in each group were routinely perfused with pronase E and type IV collagenase through portal vein catheter and the suspension was centrifuged by 11% Nycodenz density gradient to isolate hepatic stellate cells (HSCs). RT-PCR was used to analyze mRNA of MMP-2 and TIMP-1 from freshly isolated cells. Densitometric data were standardized with β-actin signals. Immunocytochemistry was performed to detect MMP-2 and TIMP-1 expression in HSC cultured for 72 h. RESULTS: Compared to group N in the 7th wk, MMP-2 and TIMP-1 mRNA increased in group C (P= 0.001/0.001) and group I (P= 0.001/0.009). The level of MMP-2 and TIMP-1 mRNA in group I was significantly lower than that in group C (P= 0.001/0.001). In the 11th wk, MMP-2 mRNA in group I was still lower than that in group C (P = 0.005), but both dropped compared with that in the 7th week (P = 0.001/0.004). TIMP-1 mRNA in group I was still lower than that in group C (P= 0.001), and increased in group C (P= 0.001) while decreased in group I (P = 0.042) compared with that in the 7th wk. Same results were found by immunocytochemistry. CONCLUSION: Expression of MMP-2 and TIMP-1 is increased in hepatic fibrosis. IL-10 exhibits an antifibrogenic effect by suppressing MMP-2 and TIMP-1 expression. 展开更多
关键词 RAT Hepatic fibrosis Hepatic stellate cells INTERLEUKIN-10 Matrix metalloproteinases-2 tissue inhibitor of metalloproteinases-1
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Matrix Metalloproteinase-2/Tissue Inhibitors of Metallo-proteinase-2 Expression in Rat Model of Chronic Allografl Nephropathy
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作者 Hequn Zou Yanling Shi Dongfeng Cu Wenying Zhou 《器官移植内科学杂志》 2012年第1期11-23,共13页
关键词 金属蛋白酶 终末期肾病 大鼠模型 抑制剂 mRNA表达 MMP-2 慢性 矩阵
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Study on Matrix Metalloproteinase-2 and Related Tissue Inhibitors in Animal Model of Chronic Allograft Nephropathy
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作者 DongFeng Gu Yanling Shi +3 位作者 Yanan Ding Atte Lotjonen Harry Holthofer Hequn Zou 《器官移植内科学杂志》 2013年第2期40-50,共11页
关键词 基质金属蛋白酶-2 终末期肾病 动物模型 组织抑制剂 移植 MRNA表达 MMP-2 慢性
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Targeting epicardial adipose tissue:A potential therapeutic strategy for heart failure with preserved ejection fraction with type 2 diabetes mellitus 被引量:1
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作者 Yu-Jiao Shi Guo-Ju Dong Ming Guo 《World Journal of Diabetes》 SCIE 2023年第6期724-740,共17页
Heart failure with preserved ejection fraction(HFpEF)is a heterogeneous syndrome with various comorbidities,multiple cardiac and extracardiac pathophysiologic abnormalities,and diverse phenotypic presentations.Since H... Heart failure with preserved ejection fraction(HFpEF)is a heterogeneous syndrome with various comorbidities,multiple cardiac and extracardiac pathophysiologic abnormalities,and diverse phenotypic presentations.Since HFpEF is a heterogeneous disease with different phenotypes,individualized treatment is required.HFpEF with type 2 diabetes mellitus(T2DM)represents a specific phenotype of HFpEF,with about 45%-50% of HFpEF patients suffering from T2DM.Systemic inflammation associated with dysregulated glucose metabolism is a critical pathological mechanism of HFpEF with T2DM,which is intimately related to the expansion and dysfunction(inflammation and hypermetabolic activity)of epicardial adipose tissue(EAT).EAT is well established as a very active endocrine organ that can regulate the pathophysiological processes of HFpEF with T2DM through the paracrine and endocrine mechanisms.Therefore,suppressing abnormal EAT expansion may be a promising therapeutic strategy for HFpEF with T2DM.Although there is no treatment specifically for EAT,lifestyle management,bariatric surgery,and some pharmaceutical interventions(anti-cytokine drugs,statins,proprotein convertase subtilisin/kexin type 9 inhibitors,metformin,glucagon-like peptide-1 receptor agonists,and especially sodium-glucose cotransporter-2 inhibitors)have been shown to attenuate the inflammatory response or expansion of EAT.Importantly,these treatments may be beneficial in improving the clinical symptoms or prognosis of patients with HFpEF.Accordingly,well-designed randomized controlled trials are needed to validate the efficacy of current therapies.In addition,more novel and effective therapies targeting EAT are needed in the future. 展开更多
关键词 Epicardial adipose tissue Heart failure with preserved ejection fraction Type 2 diabetes mellitus Inflammation Anti-hyperglycemic drugs Sodium-glucose cotransporter-2 inhibitors
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LOW DOSE PIRFENIDONE SUPPRESSES TRANSFORMING GROWTH FACTOR BETA-1 AND TISSUE INHIBITOR OF METALLOPROTEINASE-1, AND PROTECTS RATS FROM LUNG FIBROSIS INDUCED BY BLEOMYCIN 被引量:24
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作者 Xin-lun Tian Wei Yao Zi-jian Guo Li Gu Yuan-jue Zhu 《Chinese Medical Sciences Journal》 CAS CSCD 2006年第3期145-151,共7页
Objective To investigate the optimal dosage of pirfenidone for the treatment of pulmonary fibrosis induced by bleomycin in Wistar rats, and the alteration of expressions of transforming growth factor beta-1 ( TGF-β1... Objective To investigate the optimal dosage of pirfenidone for the treatment of pulmonary fibrosis induced by bleomycin in Wistar rats, and the alteration of expressions of transforming growth factor beta-1 ( TGF-β1 ), tissue inhibitor of metalloproteinase-1 ( TIMP-1 ), and matrix metalloproteinase-13 ( MMP-13 ) in lung tissue. Methods Male Wistar rats were endotracheally instilled with bleomycin or normal saline. Pirfenidone (25-800 mg · kg^-l · d^-1 ), dexamethasone (3 mg/kg), or 1% carboxymethylcellulose sodium were given daily by feed 2 days before instillation of bleomycin. Groups T7 and T14 were fed pirfenidone 50 mg · kg^-1 · d^-1 at 7 days or 14 daYs after bleomycin instillation. Lungs were harvested at 28 days after bleomycin instillation. Patholological changes in luffg tissues were evaluated with HE staining. Lung collagen was stained by sirius red and measured by content of hydroxypro- line. Expression of proteins of TGF-β1 TIMP-1, and MMP-13 were detected by Western blotting. Results At doses of 25, 50, and 100 mg· kg^- 1 · d ^- 1, pirfenidone had significant anti-fibrotic effects for bleomy- cin-induced rat pulmonary fibrosis, and these effects were most significantly attenuated at the dosage of 50 mg · kg^-1 ·d^ -1( HE: P 〈 0. 01, P 〈 0.01, and P = 0.064; sirius red: P 〈0.05, P 〈 0.01, and P 〈 0.05 ; hydroxyproline: P = 0.595, P 〈 0.01, and P = 0.976). Pirfenidone at a dosage of 50 mg · kg^- l · d^-1 inhibited protein expression of TGF-131 and TIMP-1 in lung tissue in the early phase (0.79 and 0.75 times of control group), but had no effect on ex- nr^eelnn nf MMP-13. Conclusion Low dose pirfenidone, especially at dosage of 50 mg · kg^-1 · d^-1, has significant anti-fibrotic effects on bleomycin-induced rat pulmonary fibrosis. Pirfenidone partially inhibits the enhancement of the expression of TGF-131 and TIMP-β1 in lung tissue. 展开更多
关键词 pulmonary fibrosis BLEOMYCIN pirfenidone transforming growth factor beta-1 tissue inhibitor of metalloproteinase-1
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Expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in ulcerative colitis 被引量:13
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作者 Ying-De Wang Pei-Yun Yan 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第37期6050-6053,共4页
AIM: To examine the expression of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the colonic mucosa of patients with ulcer- ative colitis (UC). METHODS: Reverse transcription-polym... AIM: To examine the expression of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the colonic mucosa of patients with ulcer- ative colitis (UC). METHODS: Reverse transcription-polymerase chain re- action (RT-PCR) and immunohistochemistry were used to study the expression of MMP-1 and TIMP-1 at both mRNA and protein levels in patients with UC and con- trols. The relationship between MMP-1 mRNA, TIMP-1 mRNA, MMP-1 mRNA/TIMP-1 mRNA ratio and the sever- ity of clinical symptoms of the patients with UC were also analyzed. RESULTS: The expression of MMP-1 mRNA and TIMP-1 mRNA in the ulcerated and inflamed colonic mucosa was signifi cantly higher than that in the non-inflamed colonic mucosa (P < 0.001), but there was no statistically signif i- cant difference in the non-inflamed colonic mucosa of UC patients and normal controls (P > 0.05). The mRNA ex- pression of MMP-1 and TIMP-1 in ulcerated colonic mu- cosa of UC patients was increased by 80-fold and 2.2-fold, respectively when compared with the normal controls. In the inflamed colonic mucosa, the increase was 30-fold and 1.6-fold, respectively. Immunohistochemical analy- sis showed that among the ulcerated, inflamed, and non-inflamed colonic mucosae of UC patients and the normal controls, the positive rate of MMP-1 expression was 87%, 87%, 40% and 35% respectively, and the positive rate of TIMP-1 expression was 89%, 89%, 80% and 75%, respectively. Furthermore, the expression of MMP-1 mRNA, TIMP-1 mRNA and the MMP-1 mRNA/ TIMP-1 mRNA ratio were correlated with the severity of clinical symptoms (P <0.05).CONCLUSION: Excessive expression of MMP-1 in the diseased colonic mucosa causes excessive hydrolysis of the extracellular matrix (ECM) and ulceration in UC pa-tients. MMP-1 mRNA, TIMP-1 mRNA and MMP-1 mRNA/ TIMP-1 mRNA ratio can be used as biomarkers to judge the severity of clinical symptoms in patients with UC. Exogenous TIMP-1 or MMP-1 inhibitor therapy is a novel treatment for patients with UC. 展开更多
关键词 Matrix metalloproteinase-1 tissue inhibitor of metalloproteinase-1 Ulcerative colitis Reverse transcriptionpolymerase chain reaction IMMUNOHISTOCHEMISTRY
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Plasma matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 as biomarkers of ulcerative colitis activity 被引量:22
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作者 Alicja Wiercinska-Drapalo Jerzy Jaroszewicz +1 位作者 Robert Flisiak Danuta Prokopowicz 《World Journal of Gastroenterology》 SCIE CAS CSCD 2003年第12期2843-2845,共3页
AIM:Overexpression of mucosal metalloproteinases(MMP) has been demonstrated recently in inflammatory bowel disease.Their activity can be counterbalanced by the tissue inhibitor of metalloproteinases(TIMP).The aim of t... AIM:Overexpression of mucosal metalloproteinases(MMP) has been demonstrated recently in inflammatory bowel disease.Their activity can be counterbalanced by the tissue inhibitor of metalloproteinases(TIMP).The aim of this study was to evaluate the effect of ulcerative colitis(UC)on MMP- 1 and TIMP-1 plasma concentrations,as two possible biomarkers of the disease activity. METHODS:MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 16 patients with endoscopically confirmed active UC. RESULTS:Plasma concentrations of both MMP-1(13.7±0.2 ng/ml)and TIMP-1(799±140 ng/ml)were significantly elevated in UC patients in comparison to healthy controls (11.9±0.9 ng/ml and 220±7 ng/ml respectively).There was no correlation between TIMP-1 and MMP-1 concentrations (r=0.02).TIMP-1 levels revealed significant positive correlations with scored endoscopic degree of mucosal injury, disease activity index and clinical activity index values as well as C-reactive protein concentration.There was no correlation between MMP-1 and laboratory,clinical or endoscopic indices of the disease activity.CONCLUSION: These results confirm the role of both MMP- 1 and TIMP-1 in the pathogenesis of ulcerative colitis. However only TIMP-1 can be useful as a biomarker of the disease activity, demonstrating association with clinical and endoscopic pictures. 展开更多
关键词 ADULT Aged Biological Markers C-Reactive Protein Colitis Ulcerative Comparative Study FEMALE Humans Interstitial Collagenase MALE Middle Aged Reference Values tissue inhibitor of metalloproteinase-1
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Interleukin-1 beta up-regulates tissue inhibitor of matrix metalloproteinase-1 mRNA and phosphorylation of c-jun N-terminal kinase and p38 in hepatic stellate cells 被引量:22
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作者 Ya-Ping Zhang Xi-Xian Yao Xia Zhao 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第9期1392-1396,共5页
AIM: To study the relationship between interleukin-lbeta (IL-1β) up-regulating tissue inhibitor of matrix metalloproteinase-1 (TIMMP-1) mRNA expression and phosphorylation of both c-jun N-terminal kinase (INK)... AIM: To study the relationship between interleukin-lbeta (IL-1β) up-regulating tissue inhibitor of matrix metalloproteinase-1 (TIMMP-1) mRNA expression and phosphorylation of both c-jun N-terminal kinase (INK) and p38 in rat heffatic stellate cells (HSC). METHODS: RT-PCR was performed to measure the expression of TIMMP-1 mRNA in rat HSC. Western blot was performed to measure IL-1β-induced JNK and p38 activities in rat HSC. RESULTS: TIMMP-1 mRNA expression (1.191± 0.079) was much higher after treatment with IL-1β (10 ng/mL) for 24 h than in control group (0.545±0.091) (P〈0.01). IL-1β activated INK and p38 in a time-dependent manner. After stimulation with IL-1β for 0, 5, 15, 30, 60 and 120 min, the INK activity was 0.982±0.299, 1.501±0.720, 2.133±0.882, 3.360±0.452, 2.181±0.789, and 1.385 ± 0.368, respectively. There was a significant difference in JNK activity at 15 min (P〈 0.01), 30 min (P〈 0.01) and 60 min (P〈0.01) in comparison to that at 0 min. The p38 activity was 1.061±0.310, 2.050±0.863, 2.380±0.573, 2.973±0.953, 2.421±0.793, and 1.755 ± 0.433 at the 6 time points (0, 5, 15, 30, 60 and 120 min) respectively. There was a significant difference in p38 activity at 5 min (P〈0.05), 15 min (P〈0.01), 30 min (P〈0.01) and 60 min (P〈0.01) compared to that at 0 min. TIMMP-1 mRNA expression trended to decrease in 3 groups pretreated with different concentrations of SP600125 (10 μmol/L, 1.022±0.113; 20 μmol/L, 0.869±0.070; 40 μmol/L, 0.666±0.123). Their decreases were all significant (P〈0.05, P〈0.01, P〈0.01) in comparison to control group (without SP600125 treatment, 1.163±0.107). In the other 3 groups pretreated with different concentrations of SB203580 (10 μmol/L, 1.507±0.099; 20 μmol/L, 1.698±0.107; 40 μmol/L, 1.857±0.054), the expression of TIMMP-1 mRNA increased. Their levels were higher than those in the control group (without SB203580 treatment, 1.027 ± 0.061) with a significant statistical significance (P〈 0.01). CONCLUSION: IL-1β has a direct action on hepatic fibrosis by up-regulating TIMMP-1 mRNA expression in ratessionin in rate HSC.JNK and p38 mitogen-activated protein kinases (MAPKs) are involved in IL-1β-induced TIMMP-1 gene expression, and play a distinct role in this process, indicating that p38 and .INK pathways cooperatively mediate TIMP-1 mRNA expression in rat HSC. 展开更多
关键词 Up-Regulation Animals ANTHRACENES Blotting Western Cell Line Enzyme inhibitors IMIDAZOLES INTERLEUKIN-1 JNK Mitogen-Activated Protein Kinases Liver Liver Cirrhosis PHOSPHORYLATION PYRIDINES RNA Messenger Rats Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Time Factors tissue inhibitor of metalloproteinase-1 p38 Mitogen-Activated Protein Kinases
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Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in early focal cerebral infarction following urokinase thrombolysis in rats 被引量:6
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作者 Yuqiang Song Hongli Zou +3 位作者 Guofeng Wang Hongxia Yang Zhaohong Xie Jianzhong Bi 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第17期1325-1330,共6页
Activity of matrix metalloproteinase-9 increases following cerebral ischemia/reperfusion, and is associated with cerebral microvascular permeability, blood-brain barrier destruction, inflammatory cell infiltration and... Activity of matrix metalloproteinase-9 increases following cerebral ischemia/reperfusion, and is associated with cerebral microvascular permeability, blood-brain barrier destruction, inflammatory cell infiltration and brain edema. Matrix metalloproteinase-9 also likely participates in thrombolysis. A rat model of middle cerebral artery infarction was established by injecting autologous blood clots into the internal carotid artery. At 3 hours following model induction, urokinase was injected into the caudal vein. Decreased neurological severity score, reduced infarct volume, and increased expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were observed in the cerebral cortex 24 hours after urokinase thrombolysis. These results suggest that urokinase can suppress damage in the acute-early stage of cerebral infarction. 展开更多
关键词 cerebral infarction UROKINASE THROMBOLYSIS matrix metalloproteinase-9 tissue inhibitor ofmetalloproteinase-1 neural regeneration
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Correlation of matrix metalloproteinase-2, -9, tissue inhibitor-1 of matrix metalloproteinase and CD44 variant 6 in head and neck cancer metastasis 被引量:8
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作者 徐娅苹 赵学群 +1 位作者 SOMMER,K. MOUBAYED,P. 《Journal of Zhejiang University Science》 CSCD 2003年第4期491-501,共11页
This study aimed to explore the molecular mechanism in tumor invasion and metastasis. The expression of matrix metalloproteinase 2, 9 (MMP 2, MMP 9), tissue inhibitor 1 of matrix metalloproteinase (TIMP 1), c... This study aimed to explore the molecular mechanism in tumor invasion and metastasis. The expression of matrix metalloproteinase 2, 9 (MMP 2, MMP 9), tissue inhibitor 1 of matrix metalloproteinase (TIMP 1), cell adhesion molecule 44 variant 6 (CD44v6), HER2/neu and p53 was investigated in 154 patients with head and neck squamous cell carcinoma (SCC) by ABC and ImmunoMax immunohistochemical method. Their clinical relevance and correlation were analysed. The expression of MMP 2, MMP 9, TIMP 1, CD44v6, HER2/neu and p53 was found in cancer cells in 87.01%, 85.71%, 68.18%, 98.05%, 55.19% and 50.65% cases respectively. Linear regression and correlation analysis revealed that there was close positive relationship ( P <0.05) between the expression of MMP 2 and MMP 9, TIMP 1 and CD44v6, HER2/neu and MMP 9, MMP 2 and p53. Up regulation of MMP 2 was accompanied by advanced T stage ( P <0.01) . There was also a trend of MMP 2 expression being related with tumor metastasis. Increased expression of HER2/neu was found in patients with tumor recurrence( P <0.05). The expression of TIMP 1 was higher in laryngeal cancer than that in pharyngeal cancer, and higher in keratinizing and non keratinizing SCC than that in basaloid SCC( P <0.05). These findings suggested that MMP 2 and MMP 9, HER2/neu and MMP 9, MMP 2 and p53 had a coordinate function in aggression of tumor; that MMP 2 had a more important function than MMP 9 in tumor invasion and metastasis; and that HER2/neu might serve as a biomarker for poor prognosis in HNSCC. 展开更多
关键词 Head and neck cancer Matrix metalloproteinase 2 9 (MMP 2 and MMP 9) tissue inhibitor 1 of matrix metalloproteinase (TIMP 1) Cell adhesion molecule 44 variant 6 (CD44 v6) HER2/NEU p53
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Expression of tissue inhibitor of metalloproteinase-1 in progression muscular dystrophy 被引量:1
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作者 Gui-Lian SUN Shuang ZHAO Ping LI Hong-Kun JIANG 《Neuroscience Bulletin》 SCIE CAS CSCD 2006年第2期85-90,共6页
Objective Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a muhifunctional protein that has thc capacity to modify cellular activities and to modulate matrix turnover. This paper revealed the contributive role o... Objective Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a muhifunctional protein that has thc capacity to modify cellular activities and to modulate matrix turnover. This paper revealed the contributive role of TIMP-1 in progressive muscular dystrophy (PMD). Methods We examined the expression and cellular localization of TIMP-1 protein using biopsied frozen muscle from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) , congenital muscular dystrophy (CMD) by immunohistochemistry, double immunofluorescence and Western blot analysis. Results The results of immunohistochemistry and double immunofluorescence showed that TIMP-1 was positive only in vascular endothelial cells of normal muscles. Immunohistochemistry and Western blot analysis showed that the staining intensity was distinctly increased in some dystrophic muscles of PMD for TIMP-1. Double immunofluorescence revealed that TIMP-1 strongly expressed in the regenerating muscle fibers, macrophages and macrophage infiltrating necrotic fibers. Some activated fibroblasts in endomysium and perimysium of DMD and CMD muscles were also positive for TIMP- 1. Conclusion The functional consequence of overexpression of TIMP-1 in the dystrophic muscles is unknown, but the elevated local expression of TIMP-1 in diseased muscles of PMD and their distinct distribution pattern provide evidence that TIMP-1 may participate in the pathogenesis of PMD. 展开更多
关键词 muscular dystrophy tissue inhibitor of metalloproteinase-1 Western blot
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Imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 may contribute to hemorrhage in cerebellar arteriovenous malformations
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作者 Fei Di Tongyan Chen +4 位作者 Hongli Li Jizong Zhao Shuo Wang Yuanli Zhao Dong Zhang 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第19期1513-1519,共7页
In this study, we determined the expression levels of matrix metalloproteinase-2 and -9 and matrix metalloproteinase tissue inhibitor-1 and -2 in brain tissues and blood plasma of patients undergoing surgery for cereb... In this study, we determined the expression levels of matrix metalloproteinase-2 and -9 and matrix metalloproteinase tissue inhibitor-1 and -2 in brain tissues and blood plasma of patients undergoing surgery for cerebellar arteriovenous malformations or primary epilepsy (control group). Immunohistochemistry and enzyme-linked immunosorbent assay revealed that the expression of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with cerebellar arteriovenous malformations than in patients with primary epilepsy. The ratio of matrix metalloproteinase-9 to matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with hemorrhagic cerebellar arteriovenous malformations compared with those with non-hemorrhagic malformations. Matrix metalloproteinase-2 and matrix metalloproteinase tissue inhibitor-2 levels were not significantly changed. These findings indicate that an imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-I, resulting in a relative overabundance of matrix metalloproteinase-9, might be the underlying mechanism of hemorrhage of cerebellar arteriovenous malformations. 展开更多
关键词 cerebellar arteriovenous malformations HEMORRHAGE matrix metalloproteinase-2 matrixmetalloproteinase-9 tissue matrix metalloproteinase inhibitor-1 tissue matrix metalloproteinaseinhibitor-2 IMMUNOHISTOCHEMISTRY enzyme-linked immunosorbent assay neural regeneration
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