Regulator of G Protein Signaling 6 Facilities Cardiac Hypertrophy by Activating Apoptosis Signal-Regulating Kinase 1-P38/c-JUN N-Terminal Kinase 1/2 Signaling.

Abstract

Background Regulator of G protein signaling 6 ( RGS 6) is an important member of the RGS family and produces pleiotropic regulatory effects on cardiac pathophysiology. However, the role of RGS 6 protein in cardiomyocytes during angiotensin II - and pressure overload-induced cardiac hypertrophy remain unknown. Methods and Results Here, we used a genetic approach to study the regulatory role of RGS 6 in cardiomyocytes during pathological cardiac hypertrophy. RGS 6 expression was significantly increased in failing human hearts and in hypertrophic murine hearts. The extent of aortic banding-induced cardiac hypertrophy, dysfunction, and fibrosis in cardiac-specific RGS 6 knockout mice was alleviated, whereas the hearts of transgenic mice with cardiac-specific RGS 6 overexpression exhibited exacerbated responses to pressure overload. Consistent with these findings, RGS 6 also facilitated an angiotensin II -induced hypertrophic response in isolated cardiomyocytes. According to the mechanistic studies, RGS 6 mediated cardiac hypertrophy by directly interacting with apoptosis signal-regulating kinase 1, which further activates the P38-c- JUN N-terminal kinase 1/2 signaling pathway. Conclusions Based on our findings, RGS 6 aggravates cardiac hypertrophy, and the RGS 6-apoptosis signal-regulating kinase 1 pathway represents a potential therapeutic target to attenuate pressure overload-driven cardiac remodeling.

• Authors: Zhijun Huang, Jingxian Shu, Weihong Jiang, Mengqing Jiang, Yao Lu, Haijiang Dai, Nana Xu, Hong Yuan, Jingjing Cai
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 7 Issue 19 Pg. e009179 (10 02 2018) ISSN: 2047-9980 [Electronic] England
• PMID: 30371330 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RGS Proteins
• Rgs6 protein, mouse
• RNA
• MAP Kinase Kinase Kinase 5
• Map3k5 protein, mouse

Topics

• Animals
• Apoptosis
• Cardiomegaly (genetics, metabolism, physiopathology)
• Cells, Cultured
• Disease Models, Animal
• Gene Expression Regulation
• Humans
• MAP Kinase Kinase Kinase 5 (genetics)
• MAP Kinase Signaling System (genetics)
• Mice
• Mice, Transgenic
• Myocytes, Cardiac (metabolism, pathology)
• RGS Proteins (biosynthesis, genetics)
• RNA (genetics)
• Signal Transduction
• Ventricular Remodeling (physiology)