血管紧张素Ⅱ对大鼠腹膜间皮细胞表达纤维连接蛋白的影响及其作用机制  

Role of MAPK signaling proteins on expression of fib ronectin in rat peritoneal mesothelial cells induced by angiotensin Ⅱ

作　　者：谢静远[1] 吴开胤[1] 王伟铭[1] 李娅[1] 任红[1] 陈楠[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院肾脏科,上海200025

出　　处：《肾脏病与透析肾移植杂志》2007年第2期146-151,共6页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：上海市重点学科基金(T0201);上海市卫生局重点学科基金(05Ⅲ001);上海市卫生局重点课题(2003ZD002)

摘　　要：目的:观察血管紧张素Ⅱ(Ang Ⅱ)对大鼠腹膜间皮细胞(RPMCs)纤维连接蛋白(FN)表达的影响,以及有丝分裂原活化蛋白激酶通路(mitogen-activated protein kinases,MAPKs)在Ang Ⅱ诱导FN表达中所起的作用。方法:酶消化法于大鼠大网膜中分离间皮细胞,以AngⅡ刺激后,分别应用real time-PCR及Western印迹法检测FN的表达情况。应用Western印迹法观察Ang Ⅱ(1μmol/L)对MAPK通路的主要信号传导蛋白ERK1/2、p38 MAPK和JNK活化的影响,并分别应用ERK1/2、p38 MAPK和JNK的抑制剂以及AngⅡ的Ⅰ型受体(AT1)阻断剂进行干预,Western印迹法观察上述抑制剂对AngⅡ诱导FN表达的影响。结果:AngⅡ促进RPMCs表达FN,活化ERK1/2和p38 MAPK信号传导通路,而不影响JNK通路的活化。ERK1/2通路抑制剂PD98059及AT1受体阻断剂(losartan)可明显抑制Ang Ⅱ诱导的FN表达增加,而p38 MAPK和JNK抑制剂对FN的表达无影响。结论:Ang Ⅱ促进RPMCs合成FN增多。AT1受体和ERK1/2通路介导了Ang Ⅱ诱导RPMCs表达FN。Objective：To investigate the effect of angiotensin Ⅱ （Ang Ⅱ ） on the expression of extracellular matrix （fibronectin FN） in rat peritoneal mesothelial cells （RPMCs）, so as to study the role of mitogen -activated protein kinases （MAPKs）on the synthesis of FN induced by Ang Ⅱ. Methodology ：The rat peritoneal mesothelial cells were isolated from the rat omenta by enzymatic disaggregation. The antagonist to type Ⅰ of Ang Ⅱ （ losartan ） and the inhibitors to ERK1/2, p38MAPK, JNK signaling pathways （PD98059, SB203580, SP600125） was added into cell supernatants lhr before Ang Ⅱ induction, respectively. The mRNA and protein levels of FN were evaluated by real - time PCR and Western Blot. The total and phosphorylated levels of ERK1/2, p38 MAPK and JNK in RPMCs were observed by Western Blot. Results：Ang Ⅱ enhanced the expression of FN and induced the activation of ERK1/2 and p38MAPK in RPMCs, but did not induced the activation of JNK pathway. Losartan and PD98059 reduced the increment of FN under Ang Ⅱ induction significantly, while SB203580 or SP600125 had no such effect. Conclusion： Ang Ⅱ enhanced the expression of FN in RPMCS, AT1 and ERK 1/2 might mediate the increment of FN synthesis induced by Ang Ⅱ in RPMCs, which was ameliorated by the antagonist of Ang Ⅱ and the inhibitors of ERK1/2, p38MAPK, and JNK signaling pathways.

关 键 词：血管紧张素Ⅱ 间皮细胞 有丝分裂原活化的蛋白激酶 腹膜纤维化 

分 类 号：R459.5[医药卫生—治疗学]