肿瘤生长因子β_1及血小板衍生生长因子对肝窦内皮细胞整合素α_6β_1及黏着斑激酶表达的影响  

The effects of TGFβ_1 and PDGF on the expression of integrin α_6β_1 and the activity of focal adhesion kinase on rat liver sinusoidal endothelial cells.

作　　者：刘小菁[1] 吴红斌 傅华 黄明慧 任敏 

机构地区：[1]华西医科大学第一医院内科实验室,成都610041 [2]华西医科大学第一医院外科实验室,成都610041 [3]华西医科大学第一医院心内科,成都610041

出　　处：《中华消化杂志》2001年第9期540-543,共4页Chinese Journal of Digestion

基　　金：国家自然科学基金 ( 3970 0 0 6 8;3980 0 0 5 4)

摘　　要：目的　观察肿瘤生长因子 β1(TGFβ1)及血小板衍生生长因子 (PDGF)对大鼠肝窦内皮细胞 (sinusoidalendothelialcell,SEC)整合素α6β1表达及黏着斑激酶 (focaladhesionkinase ,FAK)活性的影响。方法　用胶原酶原位灌注、Percoll不连续密度梯度离心法分离大鼠SEC ,并进行体外培养。采用细胞 ELISA和免疫沉淀 蛋白质酪氨酸激酶活性测定法 ,分别观察TGFβ1及PDGF对SEC表面整合素α6β1表达及FAK活性的影响。结果　经TGFβ1及PDGF作用 2 4h后 ,α6β1蛋白表达明显强于对照组(P <0 .0 5 ) ,且呈剂量依赖性。作用至 48h ,表达继续增强 ,细胞中FAK的活性也明显增高 (P <0 .0 5 ) ,虽于 48h后回落 ,但仍明显高于对照组。结论　TGFβ1及PDGF可促进SEC表面整合素α6β1的表达及FAK活性增高 ,可能是它们参与肝纤维化发生的机制之一。Objective To observe the expression of integrin α 6β 1 and the activity of focal adhesion kinase(FAK) on rat liver sinusoidal endothelial cells(SEC) treated by transforming growth factor β 1(TGFβ 1) and platelet derived growth factor(PDGF) in vitro. Methods By in situ collagenase perfusion and two step Percoll gradient centrifugation, SECs were isolated and cultured from Wistar rats. The expression of integrin α 6β 1 was determined by cell ELISA, and the activity of FAK was assessed by immunoprecipitation tyrosine kinase assay. Results The data showed that stimulation of SECs with TGFβ 1 and PDGF for 24 hrs resulted in dose dependent increase in the expression of integrin α 6β 1 in the surface of SECs. And after treated with 5 ng/ml or 10 ng/ml of TGFβ 1 and PDGF for 24 hrs, the FAK activity in SECs increased significantly while compared with the control group( P <0.05). Conclusions The expression of integrin α 6β 1 on SECs and activity of FAK in SECs were up regulated by TGFβ 1 and PDGF, and this regulation may be important in the phenotype and function change on SECs during hepatic fibrogenesis and in the pathophysiology of hepatic fibrosis.

关 键 词：肿瘤生长因子 血小板衍生生长因子 肝窦内皮细胞 整合素 黏着斑激酶 肝纤维化 

分 类 号：R575.2[医药卫生—消化系统]