Angiotensin-converting enzyme 2 ameliorates renal fibrosis by blocking the activation of mTOR/ERK signaling in apolipoprotein E-deficient mice

摘要: Angiotensin-converting enzyme 2 (ACE2) has been shown to prevent atherosclerotic lesions and renal inflammation. However, little was elucidated upon the effects mechanisms of ACE2 in kidney fibrosis progression. Here, we examined regulatory roles apolipoprotein E (ApoE) knockout (KO) mice. The ApoEKO mice were randomized daily deliver either angiotensin (Ang) II (1.5mg/kg) and/or human recombinant (rhACE2; 2mg/kg) for weeks. Downregulation upregulation phosphorylated Akt, mTOR ERK1/2 levels observed kidneys. Ang infusion led increased tubulointerstitial with greater activation mTOR/ERK1/2 signaling. II-mediated structural injury strikingly rescued by rhACE2 supplementation, associated reduced mRNA expression TGF-β1 collagen I elevated Ang-(1-7) levels. In cultured mouse fibroblasts, exposure (100nmolL(-1)) resulted obvious elevations superoxide generation, as well TGF-β1, fibronectin 1, which dramatically prevented (1mgmL(-1)) or inhibitor rapamycin (10μmolL(-1)). These protective eradicated Ang-(1-7)/Mas receptor antagonist A779 (1μmolL(-1)). Our results demonstrate importance amelioration ApoE-mutant via modulation mTOR/ERK signaling Ang-(1-7)/Ang balance, thus indicating potential therapeutic strategies enhancing action preventing atherosclerosis fibrosis-associated disorders.