ROS-EGFR-JNK-AP-1 signaling pathway involves in angiotensin Ⅱ-induced human mesangial cells proliferation / 中华肾脏病杂志

ABSTRACT

Objective To elucidate whether Ang Ⅱ indnces the proliferation of mesangial cells through ROS-EGFR-JNK-AP-1 signaling pathway. Methods The incorporation of 3H-thymidine (3H-TdR) and cell count were used to measure mesangial cell (MC) proliferation. ROS production was determined by DCFDA fluorescence. EGFR and JNK activation was assayed by Western blot. Results Ang Ⅱ significantly enhanced ROS production in mesangial cells, which was up-regulated by 2.26 folds of control group after incubation with Ang Ⅱ for 60 min. Ang Ⅱ induced EGFR phosphorylation in dose- and time-dependent manner, with the peak (3.96 folds increase) at 30 min. EGFR phosphorylation was significantly blocked by AT1R antagonist losartan, antioxidant NAC, and NADPH oxidase inhibitor apocynin and DPI. EGFR antagonist AG1478 significantly inhibited Ang Ⅱ-induced mcsangial cell proliferation. Losartan, NAC, apocynin, DPI, and AG1478 ahnost abolished Ang Ⅱ-induced JNK activation. Conclusions ROS-EGFR-JNK-AP-1 signaling pathway is involved in Ang Ⅱ-induced mesangial cell proliferation. Apocynin and AG 1478 may be used as new therapy.