Regulator of G protein signaling 5 protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload.

Proceedings of the National Academy of Sciences of the United States of America
Hong-Liang LiCongxin Huang

Abstract

The development of cardiac hypertrophy in response to increased hemodynamic load and neurohormonal stress is initially a compensatory response that may eventually lead to ventricular dilation and heart failure. Regulator of G protein signaling 5 (Rgs5) is a negative regulator of G protein-mediated signaling by inactivating Galphaq and Galphai, which mediate actions of most known vasoconstrictors. Previous studies have demonstrated that Rgs5 expresses among various cell types within mature heart and showed high levels of Rgs5 mRNA in monkey and human heart tissue by Northern blot analysis. However, the critical role of Rgs5 on cardiac remodeling remains unclear. To specifically determine the role of Rgs5 in pathological cardiac remodeling, we used transgenic mice with cardiac-specific overexpression of human Rgs5 gene and Rgs5-/- mice. Our results demonstrated that the transgenic mice were resistant to cardiac hypertrophy and fibrosis through inhibition of MEK-ERK1/2 signaling, whereas the Rgs5-/- mice displayed the opposite phenotype in response to pressure overload. These studies indicate that Rgs5 protein is a crucial component of the signaling pathway involved in cardiac remodeling and heart failure.

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Citations

Mar 1, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Zhou-Yan BianHongliang Li
Dec 29, 2011·Basic Research in Cardiology·Jinfeng XiaoHongliang Li
Feb 15, 2014·Nature Communications·Ding-Sheng JiangHongliang Li
Feb 1, 2011·The Journal of Biological Chemistry·Zhao YangKirk M Druey
May 20, 2011·American Journal of Physiology. Cell Physiology·Jagadambika J GunajeWilliam M Mahoney
Jul 23, 2011·Circulation Research·Peng Zhang, Ulrike Mende
Jan 28, 2012·American Journal of Respiratory Cell and Molecular Biology·Zhao YangKirk M Druey
Nov 13, 2012·PloS One·Mu QinCongxin Huang
Jan 15, 2014·Cardiovascular Research·Yan ZhangHongliang Li
Apr 30, 2013·Molecular Nutrition & Food Research·Wei DengQizhu Tang
Mar 8, 2011·Journal of Cellular Biochemistry·Yan ZhangGuo-Sheng Lin
Jan 1, 2014·Journal of Cellular Biochemistry·Yu LiuCongxin Huang
Aug 8, 2015·Cardiovascular Research·He HuangCongxin Huang
Feb 3, 2015·Journal of Cellular Biochemistry·Wanli LiuHe Huang
Aug 11, 2015·Frontiers in Pharmacology·Michael Mutlak, Izhak Kehat
Oct 20, 2012·Journal of Molecular and Cellular Cardiology·Mu QinCongxin Huang
Jun 7, 2018·Physiological Reviews·Steven J ForresterSatoru Eguchi
Jun 17, 2015·Hypertension·Xiao-Jing ZhangHongliang Li

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