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目的:探讨JNK-c-Jun/AP-1信号转导通路在血管紧张素Ⅱ(AngⅡ)诱导的肾小球系膜细胞(MC)增殖及细胞周期调控中的作用。方法:应用3H-胸腺嘧啶(3H-TdR)掺入法及流式细胞术测定MC增殖和细胞周期的变化。应用凝胶电泳迁移率(EMSA)和非放射性激酶活性检测法检测系膜细胞内活化蛋白-1(AP-1)及c-Jun氨基末端激酶(JNK)活性。结果:AngⅡ可呈时间依赖性地诱导MC内JNK活化,AngⅡ刺激30min后,JNK活性达到高峰,1h几乎恢复至正常水平;AngⅡ刺激后MC内AP-1活性显著增强,3H-TdR掺入量明显增加,S期和G2/M期细胞数显著增多;JNK特异性抑制剂SP600125显著抑制AngⅡ诱导AP-1活化及MC增殖。结论:AngⅡ→JNK/SAPK→c-Jun/AP-1信号通路在MC增殖中发挥一定的作用。JNK特异性抑制剂SP600125能部分抑制AngⅡ诱导的AP-1活化及细胞增殖,从而可能具有一定的治疗作用。
AIM: To investigate the role of JNK-c-Jun / AP-1 signal transduction pathway in the proliferation and cell cycle regulation of glomerular mesangial cells (MC) induced by angiotensin Ⅱ (AngⅡ). Methods: 3H-thymidine incorporation and flow cytometry were used to determine the changes of cell proliferation and cell cycle. Mesangial cell activation protein-1 (AP-1) and c-Jun N-terminal kinase (JNK) activity were measured by electrophoretic mobility shift assay (EMSA) and non-radioactive kinase assay. Results: Ang Ⅱ induced JNK activation in MCs in a time-dependent manner. After AngⅡ stimulated for 30min, the activity of JNK peaked and almost recovered to normal level in 1h. The activity of AP-1 in MC increased significantly after AngⅡ stimulation, and 3H-TdR incorporation Significantly increased, S phase and G2 / M phase cells increased significantly; JNK specific inhibitor SP600125 significantly inhibited Ang Ⅱ induced AP-1 activation and MC proliferation. Conclusion: Ang Ⅱ → JNK / SAPK → c-Jun / AP-1 signaling pathway play a role in MC proliferation. SP600125, a specific inhibitor of JNK, can partially inhibit AngⅡ-induced AP-1 activation and cell proliferation, which may have a therapeutic effect.