Regulation of angiotensin II in Ets-1 expression and its mechanism in cardiac fibroblasts

AIM To investigate the role of Ets-1 in profibrotic actions of angiotensin II (AngII) in cardiac fibroblasts (CFs). METHODS Primary cultured CFs were divided into the following groups: control, AngII treated for different time and different dose. Expression levels of Ets-1 mRNA and protein were examined using real-time RT-PCR and Western blotting. CFs were pretreated with AngII receptor blocker, inhibitors of MAPKs, PKC, and PTK. AngII-induced cell proliferation and expression of Ets-1. Connective tissue growth factor (CTGF) and plasminogen activator inhibitor-1 (PAI-1) were examined using MTT, real-time RT-PCR and Western blotting. RESULTS In growth-arrested CFs, AngII induced Ets-1 expression in a time- and concentration-dependent manner (P<0.05). Pretreatment with AngII type 1 receptor (AT1R) blocker losartan, PKC inhibitor BIM, ERK inhibitor PD98059, or JNK inhibitor SP600125 partly inhibited this induction (P<0.05) accompanied by impaired cell proliferation and production of PAI-1 and CTGF protein (P<0.05), the two downstream targets of Ets-1. CONCLUSION AngII induces Ets-1 expression through AT1R and PKC, ERK and JNK signaling pathways. Ets-1 may be an important mediator in cardiac fibrosis process by regulating CF proliferation and expression of CTGF and PAI-1.