title: Regulator of G protein signaling 3 protects against cardiac hypertrophy in mice.
abstract: Regulator of G protein signaling 3 (RGS3) is a negative regulator of G protein-mediated signaling. RGS3 has previously been shown to be expressed among various cell types within the mature heart. Basic and clinical studies have reported abnormal expressions of RGS3 in hypertrophic hearts and in the failing myocardium. However, the role of RGS3 in cardiac remodeling remains unclear. In this study, we investigated the effect of cardiac overexpression of human RGS3 on cardiac hypertrophy induced by aortic banding (AB) in RGS3 transgenic mice and wild-type littermates. The extent of cardiac hypertrophy was evaluated by echocardiography as well as pathological and molecular analyses of heart samples. RGS3 overexpression in the heart markedly reduced the extent of cardiac hypertrophy, fibrosis, and left ventricular dysfunction in response to AB. These beneficial effects were associated with the inhibition of MEK-ERK1/2 signaling. In vitro studies performed in cultured neonatal rat cardiomyocytes confirmed that RGS3 overexpression inhibits hypertrophic growth induced by angiotensin II, which was associated with the attenuation of MEK-ERK1/2 signaling. Therefore, cardiac overexpression of RGS3 inhibits maladaptive hypertrophy and fibrosis and improves cardiac function by blocking MEK-ERK1/2 signaling.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xue Yong
authors.initials: XY
authors.lastname: Zhu
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Li Hua
authors.initials: LH
authors.lastname: Guan
authors.forename: Qizhu
authors.initials: Q
authors.lastname: Tang
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Congxin
authors.initials: C
authors.lastname: Huang
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004452:Echocardiography; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D020710:RGS Proteins / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats
chemical_list: D020710:RGS Proteins; C485898:RGS3 protein, human
keywords: ERK1/2; HYPERTROPHY; RGS3; SIGNAL TRANSDUCTION