ERK和P38MAPK在转化生长因子-β_1诱导肾系膜细胞合成纤维连接蛋白中的作用

Role of ERK and P38MAPK in the regulation of TGF-β_1-inducedfibronectin production in rat mesangial cells

目的:研究细胞外信号调节激酶(ERK)和P38丝裂原活化的蛋白激酶(P38MAPK)在转化生长因子-β1(TGF-β1)诱导肾系膜细胞合成纤维连接蛋白中所介导的作用。方法:用Westernblot检测TGF-β1诱导的肾系膜细胞纤维连接蛋白合成以及ERK和P38MAPK的磷酸化。用PD98059和SB203580分别来抑制ERK和P38MAPK的活性。结果:加入TGF-β1后,系膜细胞ERK、P38MAPK磷酸化水平逐渐增加,5小时达高峰。TGF-β1显著增加系膜细胞纤维连接蛋白的表达。用PD98059预处理能增加TGF-β1引起的纤维连接蛋白合成,且具有浓度依赖性。SB203580预处理能降低TGF-β1引起的纤维连接蛋白表达,也具有浓度依赖性。结论:ERK活化可能负性调控TGF-β1引起的纤维连接蛋白表达,而P38MAPK活化对其则可能起正性调控作用。

Objective： To examine the role of extracellular signal regulated kinase （ERK） and P38 mitogen-activated protein kinase（P38MAPK） in transforming growth factor-β1（TGF-β1）- induced fibronectin protein production in rat mesangial cells. Methods： The production of fibronectin and the phosphorylation of ERK and P38MAPK induced by TGF-β1 were analysed by Western blot. PD98059 and SB203580 were used to specifically inhibit activity of ERK and P38MAPK, respectively. Results： The phosphorylation of ERK and P38MAPK was increased gradually and peaked 5 hours after TGF-β1 treatment with cultured mesangial cells. TGFv significantly increased fibronectin production in mesangial cells. Pretreatment of mesangial cells with PD98059 increased TGF-β1-induced fibronectin production in a dose dependent manner. On the contrary., SB203580 dose dependently decreased TGF-β1- stimulated fibronectin production. Conclusion： These data suggest that TGF -β1-induced activation of ERK may negatively regulate fibronectin expression, in contrast, its activation of P38MAPK may positively regulate fibronectin expression.