Diverging targets mediate the pathological roleof miR-199a-5p and miR-199a-3p by promoting cardiac hypertrophy and fibrosis

MicroRNA-199a-5p (miR-199a-5p) and -3p are enriched in the myocardium, but it is unknown whether miR-199a-5p and -3p are co-expressed in cardiac remodeling and what roles they have in cardiac hypertrophy and fibrosis. We show that miR-199a-5p and -3p are co-upregulated in the mouse and human myocard...

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Autores principales:	Ni Zeng, Yu-Qing Huang, Yu-Min Yan, Zhi-Qin Hu, Zhuo Zhang, Jia-Xin Feng, Ji-Shen Guo, Jie-Ning Zhu, Yong-Heng Fu, Xi-Pei Wang, Meng-Zhen Zhang, Jin-Zhu Duan, Xi-Long Zheng, Jin-Dong Xu, Zhi-Xin Shan
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	microRNA cardiac hypertrophy cardiac fibrosis microRNA-199a-5p microRNA-199a-3p Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/e264f9859a5f4bd783e488783367e2ec
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spelling	oai:doaj.org-article:e264f9859a5f4bd783e488783367e2ec2021-11-04T04:28:37ZDiverging targets mediate the pathological roleof miR-199a-5p and miR-199a-3p by promoting cardiac hypertrophy and fibrosis2162-253110.1016/j.omtn.2021.10.013https://doaj.org/article/e264f9859a5f4bd783e488783367e2ec2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2162253121002560https://doaj.org/toc/2162-2531MicroRNA-199a-5p (miR-199a-5p) and -3p are enriched in the myocardium, but it is unknown whether miR-199a-5p and -3p are co-expressed in cardiac remodeling and what roles they have in cardiac hypertrophy and fibrosis. We show that miR-199a-5p and -3p are co-upregulated in the mouse and human myocardium with cardiac remodeling and in Ang-II-treated neonatal mouse ventricular cardiomyocytes (NMVCs) and cardiac fibroblasts (CFs). miR-199a-5p and -3p could aggravate cardiac hypertrophy and fibrosis in vivo and in vitro. PPAR gamma coactivator 1 alpha (Ppargc1a) and sirtuin 1 (Sirt1) were identified as target genes to mediate miR-199a-5p in promoting both cardiac hypertrophy and fibrosis. However, miR-199a-3p aggravated cardiac hypertrophy and fibrosis through targeting RB transcriptional corepressor 1 (Rb1) and Smad1, respectively. Serum response factor and nuclear factor κB p65 participated in the upregulation of miR-199a-5p and -3p in Ang-II-treated NMVCs and mouse CFs, and could be conversely elevated by miR-199a-5p and -3p. Together, Ppargc1a and Sirt1, Rb1 and Smad1 mediated the pathological effect of miR-199a-5p and -3p by promoting cardiac hypertrophy and fibrosis, respectively. This study suggests a possible new strategy for cardiac remodeling therapy by inhibiting miR-199a-5p and -3p.Ni ZengYu-Qing HuangYu-Min YanZhi-Qin HuZhuo ZhangJia-Xin FengJi-Shen GuoJie-Ning ZhuYong-Heng FuXi-Pei WangMeng-Zhen ZhangJin-Zhu DuanXi-Long ZhengJin-Dong XuZhi-Xin ShanElsevierarticlemicroRNAcardiac hypertrophycardiac fibrosismicroRNA-199a-5pmicroRNA-199a-3pTherapeutics. PharmacologyRM1-950ENMolecular Therapy: Nucleic Acids, Vol 26, Iss , Pp 1035-1050 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	microRNA cardiac hypertrophy cardiac fibrosis microRNA-199a-5p microRNA-199a-3p Therapeutics. Pharmacology RM1-950
spellingShingle	microRNA cardiac hypertrophy cardiac fibrosis microRNA-199a-5p microRNA-199a-3p Therapeutics. Pharmacology RM1-950 Ni Zeng Yu-Qing Huang Yu-Min Yan Zhi-Qin Hu Zhuo Zhang Jia-Xin Feng Ji-Shen Guo Jie-Ning Zhu Yong-Heng Fu Xi-Pei Wang Meng-Zhen Zhang Jin-Zhu Duan Xi-Long Zheng Jin-Dong Xu Zhi-Xin Shan Diverging targets mediate the pathological roleof miR-199a-5p and miR-199a-3p by promoting cardiac hypertrophy and fibrosis
description	MicroRNA-199a-5p (miR-199a-5p) and -3p are enriched in the myocardium, but it is unknown whether miR-199a-5p and -3p are co-expressed in cardiac remodeling and what roles they have in cardiac hypertrophy and fibrosis. We show that miR-199a-5p and -3p are co-upregulated in the mouse and human myocardium with cardiac remodeling and in Ang-II-treated neonatal mouse ventricular cardiomyocytes (NMVCs) and cardiac fibroblasts (CFs). miR-199a-5p and -3p could aggravate cardiac hypertrophy and fibrosis in vivo and in vitro. PPAR gamma coactivator 1 alpha (Ppargc1a) and sirtuin 1 (Sirt1) were identified as target genes to mediate miR-199a-5p in promoting both cardiac hypertrophy and fibrosis. However, miR-199a-3p aggravated cardiac hypertrophy and fibrosis through targeting RB transcriptional corepressor 1 (Rb1) and Smad1, respectively. Serum response factor and nuclear factor κB p65 participated in the upregulation of miR-199a-5p and -3p in Ang-II-treated NMVCs and mouse CFs, and could be conversely elevated by miR-199a-5p and -3p. Together, Ppargc1a and Sirt1, Rb1 and Smad1 mediated the pathological effect of miR-199a-5p and -3p by promoting cardiac hypertrophy and fibrosis, respectively. This study suggests a possible new strategy for cardiac remodeling therapy by inhibiting miR-199a-5p and -3p.
format	article
author	Ni Zeng Yu-Qing Huang Yu-Min Yan Zhi-Qin Hu Zhuo Zhang Jia-Xin Feng Ji-Shen Guo Jie-Ning Zhu Yong-Heng Fu Xi-Pei Wang Meng-Zhen Zhang Jin-Zhu Duan Xi-Long Zheng Jin-Dong Xu Zhi-Xin Shan
author_facet	Ni Zeng Yu-Qing Huang Yu-Min Yan Zhi-Qin Hu Zhuo Zhang Jia-Xin Feng Ji-Shen Guo Jie-Ning Zhu Yong-Heng Fu Xi-Pei Wang Meng-Zhen Zhang Jin-Zhu Duan Xi-Long Zheng Jin-Dong Xu Zhi-Xin Shan
author_sort	Ni Zeng
title	Diverging targets mediate the pathological roleof miR-199a-5p and miR-199a-3p by promoting cardiac hypertrophy and fibrosis
title_short	Diverging targets mediate the pathological roleof miR-199a-5p and miR-199a-3p by promoting cardiac hypertrophy and fibrosis
title_full	Diverging targets mediate the pathological roleof miR-199a-5p and miR-199a-3p by promoting cardiac hypertrophy and fibrosis
title_fullStr	Diverging targets mediate the pathological roleof miR-199a-5p and miR-199a-3p by promoting cardiac hypertrophy and fibrosis
title_full_unstemmed	Diverging targets mediate the pathological roleof miR-199a-5p and miR-199a-3p by promoting cardiac hypertrophy and fibrosis
title_sort	diverging targets mediate the pathological roleof mir-199a-5p and mir-199a-3p by promoting cardiac hypertrophy and fibrosis
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/e264f9859a5f4bd783e488783367e2ec
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Diverging targets mediate the pathological roleof miR-199a-5p and miR-199a-3p by promoting cardiac hypertrophy and fibrosis

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