Regulator of G protein signalling 14 attenuates cardiac remodelling through the MEK-ERK1/2 signalling pathway.
In the past 10 years, several publications have highlighted the role of the regulator of G protein signalling (RGS) family in multiple diseases, including cardiovascular diseases. As one of the multifunctional family members, RGS14 is involved in various biological processes, such as synaptic plasticity, cell division, and phagocytosis. However, the role of RGS14 in cardiovascular diseases remains unclear. In the present study, we used a genetic approach to examine the role of RGS14 in pathological cardiac remodelling in vivo and in vitro. We observed that RGS14 was down-regulated in human failing hearts, murine hypertrophic hearts, and isolated hypertrophic cardiomyocytes. Moreover, the extent of aortic banding-induced cardiac hypertrophy and fibrosis was exacerbated in RGS14 knockout mice, whereas RGS14 transgenic mice exhibited a significantly alleviated response to pressure overload. Furthermore, research of the underlying mechanism revealed that the RGS14-dependent rescue of cardiac remodelling was attributed to the abrogation of mitogen-activated protein kinase (MEK)-extracellular signal-regulated protein kinase (ERK) 1/2 signalling. The results showed that constitutive activation of MEK1 nullified the cardiac protection in RGS14 transgenic mice, and inhibition of MEK-ERK1/2 by U0126 reversed RGS14 deletion-related hypertrophic aggravation. These results demonstrated that RGS14 attenuated the development of cardiac remodelling through MEK-ERK1/2 signalling. RGS14 exhibited great potential as a target for the treatment of pathological cardiac remodelling.
Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, 138 Tong-Zi-Po Road, Changsha, 410013, Hunan, People's Republic of China.|Department of Cardiology, The Third Xiangya Hospital, Central South University, 138 Tong-Zi-Po Road, Changsha, 410013, Hunan, People's Republic of China.
Ying
Y
Li
Department of Cardiology, The Third Xiangya Hospital, Central South University, 138 Tong-Zi-Po Road, Changsha, 410013, Hunan, People's Republic of China.
Xiao-Hong
XH
Tang
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, 410078, Hunan, People's Republic of China.
Xiao-Hui
XH
Li
Department of Cardiology, The Third Xiangya Hospital, Central South University, 138 Tong-Zi-Po Road, Changsha, 410013, Hunan, People's Republic of China.
Hai-Jiang
HJ
Dai
Department of Cardiology, The Third Xiangya Hospital, Central South University, 138 Tong-Zi-Po Road, Changsha, 410013, Hunan, People's Republic of China.
Ru-Jia
RJ
Miao
Department of Cardiology, The Third Xiangya Hospital, Central South University, 138 Tong-Zi-Po Road, Changsha, 410013, Hunan, People's Republic of China.
Jing-Jing
JJ
Cai
Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, 138 Tong-Zi-Po Road, Changsha, 410013, Hunan, People's Republic of China.
Zhi-Jun
ZJ
Huang
Department of Cardiology, The Third Xiangya Hospital, Central South University, 138 Tong-Zi-Po Road, Changsha, 410013, Hunan, People's Republic of China.
Alex F
AF
Chen
Center for Experimental Medicine Research, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, People's Republic of China.
Xiao-Wei
XW
Xing
Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, 138 Tong-Zi-Po Road, Changsha, 410013, Hunan, People's Republic of China. luyao0719@163.com.
Yao
Y
Lu
Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, 138 Tong-Zi-Po Road, Changsha, 410013, Hunan, People's Republic of China. yuanhongxy3@163.com.|Department of Cardiology, The Third Xiangya Hospital, Central South University, 138 Tong-Zi-Po Road, Changsha, 410013, Hunan, People's Republic of China. yuanhongxy3@163.com.
Hong
H
Yuan
D000818:Animals; D015153:Blotting, Western; D006332:Cardiomegaly / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020710:RGS Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020257:Ventricular Remodeling / Q000502:physiology*
D020710:RGS Proteins
Cardiac dysfunction; Cardiac remodelling; ERK1/2; MEK1/2; RGS14