Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity...Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and permeability.Methods We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)challenge.In a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive days.Cultured pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic investigations.The effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also examined.Results CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways.Conclusions Pericytes are protective against sepsis through regulating vascular reactivity and barrier function.Possible mechanisms include both direct colonization of microvasculature and secretion of PCMVs.展开更多
Objective:To investigate the relationship between the expression of epidermal growth factor receptor(ECFR) in gastric cancer and the clinicopalhological features and prognosis. Methods:A total of 78 paraffin specimens...Objective:To investigate the relationship between the expression of epidermal growth factor receptor(ECFR) in gastric cancer and the clinicopalhological features and prognosis. Methods:A total of 78 paraffin specimens of gastric cancer operation were collected.The immunohistochemical method was used to detect the expression of ECFR in 78 cases of gastric cancer and 20 cases of adjacent normal tissue.The relationship between the high expression of ECFR and clinicopathological features was analyzed.Results:ECFR positive expression rate in the 78 cases of gastric cancer tissue was 57.7%(43/78),while ECFR was not expressed in 20 cases of adjacent normal tissue.The high ECFR expression was positively correlated with the position of gastric cancer,tumor size,cell differentiation,invasive depth,lymph node metastasis and TNM staging,yet having no obvious relation with gender or age.Conclusions:ECFR expression level in gastric cancer is closely related to the incidence and development of gastric cancer,which can provide a theoretical basis for the targeted therapy for gastric cancer with ECFR as the target.展开更多
Pericyte,a kind of pluripotent cell,may regulate the irigation flow and permeability of microcirculation.Pericytes are similar to the smooth muscle cells,which express several kinds of contractile proteins and have co...Pericyte,a kind of pluripotent cell,may regulate the irigation flow and permeability of microcirculation.Pericytes are similar to the smooth muscle cells,which express several kinds of contractile proteins and have contractility.The dysfunction of pericytes is related to many microvascular diseases,including hypoxia,hypertension,diabetic retinopathy,fibrosis,inflammation,Alzheimer's disease,multiple scle-rosis,and tumor formation.For a long time,their existence and function have been neglected.The distribution,structure,biomarker,related signaling pathways as well as the roles of pericytes on vascular diseases will be introduced in this review.展开更多
基金supported by the Key Projects and Innovation Group of National Natural Science Foundation of China(81830065),the Innovation Groups of NSFC(81721001),and the Young Scientists Fund(82102279).
文摘Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and permeability.Methods We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)challenge.In a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive days.Cultured pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic investigations.The effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also examined.Results CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways.Conclusions Pericytes are protective against sepsis through regulating vascular reactivity and barrier function.Possible mechanisms include both direct colonization of microvasculature and secretion of PCMVs.
基金supported by the Science and Technology Development Plan of Henan provinre(No.122102310245)Fund for Key Medical Science and Technology Program of Henan province(No.201203055)
文摘Objective:To investigate the relationship between the expression of epidermal growth factor receptor(ECFR) in gastric cancer and the clinicopalhological features and prognosis. Methods:A total of 78 paraffin specimens of gastric cancer operation were collected.The immunohistochemical method was used to detect the expression of ECFR in 78 cases of gastric cancer and 20 cases of adjacent normal tissue.The relationship between the high expression of ECFR and clinicopathological features was analyzed.Results:ECFR positive expression rate in the 78 cases of gastric cancer tissue was 57.7%(43/78),while ECFR was not expressed in 20 cases of adjacent normal tissue.The high ECFR expression was positively correlated with the position of gastric cancer,tumor size,cell differentiation,invasive depth,lymph node metastasis and TNM staging,yet having no obvious relation with gender or age.Conclusions:ECFR expression level in gastric cancer is closely related to the incidence and development of gastric cancer,which can provide a theoretical basis for the targeted therapy for gastric cancer with ECFR as the target.
基金This study was supported by the Key Projects and innovation group of National Natural Science Foundation of China(81830065,81721001).
文摘Pericyte,a kind of pluripotent cell,may regulate the irigation flow and permeability of microcirculation.Pericytes are similar to the smooth muscle cells,which express several kinds of contractile proteins and have contractility.The dysfunction of pericytes is related to many microvascular diseases,including hypoxia,hypertension,diabetic retinopathy,fibrosis,inflammation,Alzheimer's disease,multiple scle-rosis,and tumor formation.For a long time,their existence and function have been neglected.The distribution,structure,biomarker,related signaling pathways as well as the roles of pericytes on vascular diseases will be introduced in this review.
