c-Jun氨基末端激酶在转化生长因子-β_1诱导肾系膜细胞合成纤维连接蛋白中的作用

Role of c-Jun N-terminal kinase in the regulation of TGF-β_1-induced fibronectin production in rat mesangial cells

目的研究c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)在转化生长因子-1β(transforminggrowth factor-β1,TGF-β1)诱导肾系膜细胞合成纤维连接蛋白(fibronectin)中所介导的作用。方法用蛋白免疫印迹法检测TGF-β1诱导的肾系膜细胞纤维连接蛋白合成以及JNK的磷酸化。用SP600125来抑制JNK的活性。结果加入TGF-β1后,系膜细胞JNK磷酸化水平逐渐增加,5 h时达高峰,TGF-1β显著增加系膜细胞纤维连接蛋白的表达。用SP600125预处理系膜细胞能增加TGF-β1引起的纤维连接蛋白表达,且具有剂量依赖性。结论JNK活化可能负性调控TGF-β1引起的纤维连接蛋白表达。

Objective To examine the role of c - Jun N - terminal kinase （JNK） in transforming growth factor - β1 （TGF - β1 ） - induced fibronectin protein production in rat mesangial cells. Methods The expression of fibronectin and phosphorylation of JNK induced by TGF -β1 were tested by Western blot. SP600125 was used to specifically inhibit the activity of JNK. Results The phosphorylation of JNK was increased gradually and peaked 5 hours after the cultured mesangial cells were treated with TGF- β1 ; and TGF - β1 significantly increased fibronectin production in mesangial cells. However, pretreatment of mesangial cells with SP600125 could dose - dependently increase TGF- β1 - induced fibronectin production. Conclusion These data suggest that TGF- β1 - induced activation of jNK may negatively regulate fibronectin expression.