title: Regulator of G-Protein Signaling 10 Negatively Regulates Cardiac Remodeling by Blocking Mitogen-Activated Protein Kinase-Extracellular Signal-Regulated Protein Kinase 1/2 Signaling.
abstract: Regulator of G-protein signaling 10 (RGS10) is an important member of the RGS family and produces biological effects in multiple organs. We used a genetic approach to study the role of RGS10 in the regulation of pathological cardiac hypertrophy and found that RGS10 can negatively influence pressure overload-induced cardiac remodeling. RGS10 expression was markedly decreased in failing human hearts and hypertrophic murine hearts. The extent of aortic banding-induced cardiac hypertrophy, dysfunction, and fibrosis in RGS10-knockout mice was exacerbated, whereas the heart of transgenic mice with cardiac-specific RGS10 overexpression exhibited an alleviated response to pressure overload. Consistently, RGS10 also inhibited an angiotensin II-induced hypertrophic response in isolated cardiomyocytes. Mechanistically, cardiac remodeling improvement elicited by RGS10 was associated with the abrogation of mitogen-activated protein kinase kinase 1/2-extracellular signal-regulated protein kinase 1/2 signaling. Furthermore, the inhibition of mitogen-activated protein kinase kinase-extracellular signal-regulated protein kinase 1/2 transduction abolished RGS10 deletion-induced hypertrophic aggravation. These findings place RGS10 and its downstream signaling mitogen-activated protein kinase kinase-extracellular signal-regulated protein kinase 1/2 as crucial regulators of pathological cardiac hypertrophy after pressure overload and identify this pathway as a potential therapeutic target to attenuate the pressure overload-driven cardiac remodeling.
authors.affiliation: From the Department of Cardiology (R.M., H.Z., A.F.C., X.T., J.C., H.Y.) and Center of Clinical Pharmacology (Y.L., X.X., Y.L., Z.H., Y.H., J.C., H.Y.), the Third Xiangya Hospital, Central South University, Changsha, China; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China (H.L.); and Cardiovascular Research Institute of Wuhan University, Wuhan, China (H.L.).
authors.forename: Rujia
authors.initials: R
authors.lastname: Miao
authors.affiliation: From the Department of Cardiology (R.M., H.Z., A.F.C., X.T., J.C., H.Y.) and Center of Clinical Pharmacology (Y.L., X.X., Y.L., Z.H., Y.H., J.C., H.Y.), the Third Xiangya Hospital, Central South University, Changsha, China; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China (H.L.); and Cardiovascular Research Institute of Wuhan University, Wuhan, China (H.L.).
authors.forename: Yao
authors.initials: Y
authors.lastname: Lu
authors.affiliation: From the Department of Cardiology (R.M., H.Z., A.F.C., X.T., J.C., H.Y.) and Center of Clinical Pharmacology (Y.L., X.X., Y.L., Z.H., Y.H., J.C., H.Y.), the Third Xiangya Hospital, Central South University, Changsha, China; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China (H.L.); and Cardiovascular Research Institute of Wuhan University, Wuhan, China (H.L.).
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xing
authors.affiliation: From the Department of Cardiology (R.M., H.Z., A.F.C., X.T., J.C., H.Y.) and Center of Clinical Pharmacology (Y.L., X.X., Y.L., Z.H., Y.H., J.C., H.Y.), the Third Xiangya Hospital, Central South University, Changsha, China; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China (H.L.); and Cardiovascular Research Institute of Wuhan University, Wuhan, China (H.L.).
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: From the Department of Cardiology (R.M., H.Z., A.F.C., X.T., J.C., H.Y.) and Center of Clinical Pharmacology (Y.L., X.X., Y.L., Z.H., Y.H., J.C., H.Y.), the Third Xiangya Hospital, Central South University, Changsha, China; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China (H.L.); and Cardiovascular Research Institute of Wuhan University, Wuhan, China (H.L.).
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Huang
authors.affiliation: From the Department of Cardiology (R.M., H.Z., A.F.C., X.T., J.C., H.Y.) and Center of Clinical Pharmacology (Y.L., X.X., Y.L., Z.H., Y.H., J.C., H.Y.), the Third Xiangya Hospital, Central South University, Changsha, China; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China (H.L.); and Cardiovascular Research Institute of Wuhan University, Wuhan, China (H.L.).
authors.forename: Hua
authors.initials: H
authors.lastname: Zhong
authors.affiliation: From the Department of Cardiology (R.M., H.Z., A.F.C., X.T., J.C., H.Y.) and Center of Clinical Pharmacology (Y.L., X.X., Y.L., Z.H., Y.H., J.C., H.Y.), the Third Xiangya Hospital, Central South University, Changsha, China; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China (H.L.); and Cardiovascular Research Institute of Wuhan University, Wuhan, China (H.L.).
authors.forename: Yun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: From the Department of Cardiology (R.M., H.Z., A.F.C., X.T., J.C., H.Y.) and Center of Clinical Pharmacology (Y.L., X.X., Y.L., Z.H., Y.H., J.C., H.Y.), the Third Xiangya Hospital, Central South University, Changsha, China; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China (H.L.); and Cardiovascular Research Institute of Wuhan University, Wuhan, China (H.L.).
authors.forename: Alex F
authors.initials: AF
authors.lastname: Chen
authors.affiliation: From the Department of Cardiology (R.M., H.Z., A.F.C., X.T., J.C., H.Y.) and Center of Clinical Pharmacology (Y.L., X.X., Y.L., Z.H., Y.H., J.C., H.Y.), the Third Xiangya Hospital, Central South University, Changsha, China; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China (H.L.); and Cardiovascular Research Institute of Wuhan University, Wuhan, China (H.L.).
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Tang
authors.affiliation: From the Department of Cardiology (R.M., H.Z., A.F.C., X.T., J.C., H.Y.) and Center of Clinical Pharmacology (Y.L., X.X., Y.L., Z.H., Y.H., J.C., H.Y.), the Third Xiangya Hospital, Central South University, Changsha, China; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China (H.L.); and Cardiovascular Research Institute of Wuhan University, Wuhan, China (H.L.).
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.affiliation: From the Department of Cardiology (R.M., H.Z., A.F.C., X.T., J.C., H.Y.) and Center of Clinical Pharmacology (Y.L., X.X., Y.L., Z.H., Y.H., J.C., H.Y.), the Third Xiangya Hospital, Central South University, Changsha, China; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China (H.L.); and Cardiovascular Research Institute of Wuhan University, Wuhan, China (H.L.). yuanhongxy3@163.com caijingjing83@hotmail.com.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Cai
authors.affiliation: From the Department of Cardiology (R.M., H.Z., A.F.C., X.T., J.C., H.Y.) and Center of Clinical Pharmacology (Y.L., X.X., Y.L., Z.H., Y.H., J.C., H.Y.), the Third Xiangya Hospital, Central South University, Changsha, China; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China (H.L.); and Cardiovascular Research Institute of Wuhan University, Wuhan, China (H.L.). yuanhongxy3@163.com caijingjing83@hotmail.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins
keywords: angiotensin II; cardiomegaly; extracellular signal-regulated MAP kinases; mitogen-activated protein kinase kinases; signal transduction