Angiotensin-(1-7)/Mas Axis Opposes Angiotensin Ⅱ-induced Signaling By Activating Src Homology2-containing Inositol Phosphatase1

Objective： Angiotensin(1-7)[Ang(1-7)], acting through the Masreceptor, inhibits the actions of angiotensin Ⅱ (Ang Ⅱ). While the specificmolecular mechanisms for this are unclear. Therefore we sought to explorethe mechanism of Ang(1-7) opposing Ang Ⅱ-induced signaling responses inrat cardiac fibroblasts.Methods：Primary culture of neonatal Sprague-Dawley rats cardiacfibroblasts were treated separately with different interventions to determinethis issue. The expression levels of c-src tyrosine kinase(c-Src)，phospho-c-Src(p-c-Src)，extracellular signal-related kinase1/2(ERK1/2)，phospho-ERK1/2(p-ERK1/2)，alpha-smooth muscle actin(α-SMA)，andtransforming growth factor-β1(TGF-β1) were assayed by immunoblot.Results：Ang Ⅱ increased p-c-Src and the ratio of (p-c-Src)/(Src)，p-ERK1/2and the ratio of (p-ERK1/2)/(ERK1/2)，α-SMA and TGF-β1.While overexpression of SHP-1(Src-homology Domain2ContainingProtein Tyrosine Phosphatase-1) could attenuate the ANG Ⅱ-stimulated p-c-Src,itsdownstreammolecules ERK1/2,α-SMA and TGF-β1，and theseeffects were also inhibited by the specific inhibitor of SHP-1, sodiumstibogluconate(S).Conclusions： Overexpression of SHP-1attenuated the ANGⅡ-stimulated p-c-Src, its downstream molecules ERK1/2, α-SMA andTGF-β1, and these effects were also inhibited by the specific inhibitor ofSHP-1, sodium stibogluconate. Therefore the Ang(1-7)/Mas axisantagonizing AngⅡ-stimulated signaling may be through activating SHP-1.