ROS-EGFR-JNK-AP-1 signaling pathway involves in angiotensin Ⅱ-induced human mesangial cells proliferation
- VernacularTitle:血管紧张素Ⅱ通过ROS-EGFR-JNK-AP-1信号通路诱导肾小球系膜细胞增殖
- Author:
Songming HUANG
;
Aihua ZHANG
;
Guixia DING
;
Weizhen ZHANG
;
Huaying BAO
;
Hongmei WU
;
Ronghua CHEN
- Publication Type:Journal Article
- Keywords:
Mesangial cell;
Angiotensin Ⅱ;
Nicotinamide adenine dinucleotidephosphate-oxidase;
Epidermal growth factor receptor;
c-Jun aminoterminal kinase
- From:
Chinese Journal of Nephrology
2008;24(9):642-646
- CountryChina
- Language:Chinese
-
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.
