Fas配体对NIH3T3增殖和胶原表达的信号机制研究  

Role of Fas ligand in the proliferation and expression of collagen on NIH3T3 cell and its signaling mechanism

作　　者：姚三巧[1,4] LU Yongju WANG Liying Rojanasakul Anand Iyer Neelam Azad Yon Rojanasakul 

机构地区：[1]华北煤炭医学院劳动卫生与环境卫生学科,河北唐山063000 [2]美国西弗吉尼亚大学基础药学院,Morgantown,WV26505 USA [3]美国国立职业安全与卫生研究所,Morgantown,WV26505,USA [4]河北省煤矿卫生与安全实验室,唐山063000

出　　处：《中国职业医学》2010年第2期91-94,共4页China Occupational Medicine

基　　金：美国国立卫生研究院(NIH)基金项目(R01HL076340);国家自然科学基金项目(30671741)

摘　　要：目的探讨Fas配体(FasL)对小鼠成纤维细胞NIH3T3增殖和胶原表达的影响及其信号调控机制。方法采用鼠成纤维细胞系HIN3T3,以FasL为诱导剂,采用抑制剂技术和Western blot技术观察NIH3T3的增殖及胶原表达情况,同时探讨磷脂酰肌醇3-激酶(PI3K)/Akt、有丝分裂原活化蛋白(MAPK)/P38、MAPK/ERK信号通路在NIH3T3增殖和胶原表达中的作用。结果研究发现低剂量的FasL可调节3T3的生长,表现为细胞数量和胶原表达水平均随FasL剂量的增加而增加,且存在剂量-效应和时间-效应;MAPK/P38及PI3K/Akt信号通路对NIH3T3的增殖具有调控作用,MAPK/P38及MAPK/ERK信号通路可调控NIH3T3胶原表达。结论Fas/FasL系统对成纤维细胞增殖和胶原表达起促进作用;FasL主要通过PI3K/Akt、MAPK/P38信号通路对成纤维细胞增殖起调控作用;通过MAPK/P38及MAPK/ERK信号通路调节成纤维细胞的胶原表达。Objective To reveal the role of Fas ligand （FasL） in triggering fibroblast proliferation and collagen expression of NIH3T3 cell and the signaling mechanism.Methods NIH3T3 was chosen as the targeted fibroblast cell,and FasL as the trigger.Inhibitors used to block the signal transduction and western blot were applied to observe the cell proliferation and collagen expression during the experiment.Results It was shown that 3T3 was regulated by low dose of FasL,both of the cell number and collagen expression increased with the doses of FasL increased.With the incubation time increased,the NIH3T3 number and collagen expression were increased.There were dose-response and time-response relationships between FasL and the NIH3T3 number and collagen expression.Conclusion It suggests that FasL can regulate fibroblast proliferation and collagen expression,indicating that it can trigger fibrosis.The signaling mechanism is via PI3K/Akt,MAPK/P38 and MAPK/ERK signal transduction pathway.

关 键 词：FAS配体 NIH3T3 增殖 Ⅰ、Ⅲ型胶原 信号转导 

分 类 号：R135.2[医药卫生—劳动卫生]