G Protein–Coupled Estrogen Receptor 30 Reduces Transverse Aortic Constriction–Induced Myocardial Fibrosis in Aged Female Mice by Inhibiting the ERK1/2 -MMP-9 Signaling Pathway

The incidence of cardiovascular diseases was significantly increased in postmenopausal women. The protection of estrogen in the cardiovascular system has been further reported for decades. Although menopausal hormone therapy has been used in many clinical trials, the debatable results indicate that...

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Autores principales:	Xiaowu Wang, Jipeng Ma, Shuaishuai Zhang, Zilin Li, Ziwei Hong, Liqing Jiang, Weixun Duan, Jincheng Liu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	G protein–coupled estrogen receptor 30 (GPR30) transverse aortic constriction MMP-9 aged female cardiac fibrosis Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/f2b43bf790a04a4db24683e3e1dc2ca7
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spelling	oai:doaj.org-article:f2b43bf790a04a4db24683e3e1dc2ca72021-11-05T15:25:46ZG Protein–Coupled Estrogen Receptor 30 Reduces Transverse Aortic Constriction–Induced Myocardial Fibrosis in Aged Female Mice by Inhibiting the ERK1/2 -MMP-9 Signaling Pathway1663-981210.3389/fphar.2021.731609https://doaj.org/article/f2b43bf790a04a4db24683e3e1dc2ca72021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.731609/fullhttps://doaj.org/toc/1663-9812The incidence of cardiovascular diseases was significantly increased in postmenopausal women. The protection of estrogen in the cardiovascular system has been further reported for decades. Although menopausal hormone therapy has been used in many clinical trials, the debatable results indicate that the studies for elucidating the precise molecular mechanism are urgently required. G protein–coupled estrogen receptor 30 (GPR30) is a membrane receptor of estrogen and displays protective roles in diverse cardiovascular diseases. Previous studies have revealed that ERK1/2-mediated MMP-9 signaling was involved in ischemic heart diseases. However, the role of ERK1/2-mediated MMP-9 signaling in the protection of GPR30 against cardiac hypertrophy in aged female mice has not been investigated. Our present study demonstrated that GPR30 overexpression and its agonist G1 co-administration reduced transverse aortic constriction–induced myocardial fibrosis and preserved cardiac function in aged female mice. MMP-9 expression was markedly increased via ERK1/2 phosphorylation in transverse aortic constriction–injured myocardium of aged female mice. Further results showed that GPR30/G1 activation decreased MMP-9 expression via ERK1/2 inhibition, which further reduced TGF-β1 expression. Inhibition of the ERK1/2 signaling pathway by its inhibitor PD98059 suppressed the induction of the cardiomyocyte MMP-9 level caused by the GRP30 antagonist G15 and inhibited TGF-β1 expression in cardiac fibroblast in vitro. In summary, our results from in vivo and in vitro studies indicated that GPR30 activation inhibited myocardial fibrosis and preserved cardiac function via inhibiting ERK-mediated MMP-9 expression. Thus, the present study may provide the novel drug targets for prevention and treatment of cardiac pathological hypertrophy in postmenopausal women.Xiaowu WangJipeng MaShuaishuai ZhangZilin LiZiwei HongLiqing JiangWeixun DuanJincheng LiuFrontiers Media S.A.articleG protein–coupled estrogen receptor 30 (GPR30)transverse aortic constrictionMMP-9aged femalecardiac fibrosisTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	G protein–coupled estrogen receptor 30 (GPR30) transverse aortic constriction MMP-9 aged female cardiac fibrosis Therapeutics. Pharmacology RM1-950
spellingShingle	G protein–coupled estrogen receptor 30 (GPR30) transverse aortic constriction MMP-9 aged female cardiac fibrosis Therapeutics. Pharmacology RM1-950 Xiaowu Wang Jipeng Ma Shuaishuai Zhang Zilin Li Ziwei Hong Liqing Jiang Weixun Duan Jincheng Liu G Protein–Coupled Estrogen Receptor 30 Reduces Transverse Aortic Constriction–Induced Myocardial Fibrosis in Aged Female Mice by Inhibiting the ERK1/2 -MMP-9 Signaling Pathway
description	The incidence of cardiovascular diseases was significantly increased in postmenopausal women. The protection of estrogen in the cardiovascular system has been further reported for decades. Although menopausal hormone therapy has been used in many clinical trials, the debatable results indicate that the studies for elucidating the precise molecular mechanism are urgently required. G protein–coupled estrogen receptor 30 (GPR30) is a membrane receptor of estrogen and displays protective roles in diverse cardiovascular diseases. Previous studies have revealed that ERK1/2-mediated MMP-9 signaling was involved in ischemic heart diseases. However, the role of ERK1/2-mediated MMP-9 signaling in the protection of GPR30 against cardiac hypertrophy in aged female mice has not been investigated. Our present study demonstrated that GPR30 overexpression and its agonist G1 co-administration reduced transverse aortic constriction–induced myocardial fibrosis and preserved cardiac function in aged female mice. MMP-9 expression was markedly increased via ERK1/2 phosphorylation in transverse aortic constriction–injured myocardium of aged female mice. Further results showed that GPR30/G1 activation decreased MMP-9 expression via ERK1/2 inhibition, which further reduced TGF-β1 expression. Inhibition of the ERK1/2 signaling pathway by its inhibitor PD98059 suppressed the induction of the cardiomyocyte MMP-9 level caused by the GRP30 antagonist G15 and inhibited TGF-β1 expression in cardiac fibroblast in vitro. In summary, our results from in vivo and in vitro studies indicated that GPR30 activation inhibited myocardial fibrosis and preserved cardiac function via inhibiting ERK-mediated MMP-9 expression. Thus, the present study may provide the novel drug targets for prevention and treatment of cardiac pathological hypertrophy in postmenopausal women.
format	article
author	Xiaowu Wang Jipeng Ma Shuaishuai Zhang Zilin Li Ziwei Hong Liqing Jiang Weixun Duan Jincheng Liu
author_facet	Xiaowu Wang Jipeng Ma Shuaishuai Zhang Zilin Li Ziwei Hong Liqing Jiang Weixun Duan Jincheng Liu
author_sort	Xiaowu Wang
title	G Protein–Coupled Estrogen Receptor 30 Reduces Transverse Aortic Constriction–Induced Myocardial Fibrosis in Aged Female Mice by Inhibiting the ERK1/2 -MMP-9 Signaling Pathway
title_short	G Protein–Coupled Estrogen Receptor 30 Reduces Transverse Aortic Constriction–Induced Myocardial Fibrosis in Aged Female Mice by Inhibiting the ERK1/2 -MMP-9 Signaling Pathway
title_full	G Protein–Coupled Estrogen Receptor 30 Reduces Transverse Aortic Constriction–Induced Myocardial Fibrosis in Aged Female Mice by Inhibiting the ERK1/2 -MMP-9 Signaling Pathway
title_fullStr	G Protein–Coupled Estrogen Receptor 30 Reduces Transverse Aortic Constriction–Induced Myocardial Fibrosis in Aged Female Mice by Inhibiting the ERK1/2 -MMP-9 Signaling Pathway
title_full_unstemmed	G Protein–Coupled Estrogen Receptor 30 Reduces Transverse Aortic Constriction–Induced Myocardial Fibrosis in Aged Female Mice by Inhibiting the ERK1/2 -MMP-9 Signaling Pathway
title_sort	g protein–coupled estrogen receptor 30 reduces transverse aortic constriction–induced myocardial fibrosis in aged female mice by inhibiting the erk1/2 -mmp-9 signaling pathway
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/f2b43bf790a04a4db24683e3e1dc2ca7
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G Protein–Coupled Estrogen Receptor 30 Reduces Transverse Aortic Constriction–Induced Myocardial Fibrosis in Aged Female Mice by Inhibiting the ERK1/2 -MMP-9 Signaling Pathway

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