Metformin accelerates zebrafish heart regeneration by inducing autophagy

Abstract Metformin is one of the most widely used drugs for type 2 diabetes and it also exhibits cardiovascular protective activity. However, the underlying mechanism of its action is not well understood. Here, we used an adult zebrafish model of heart cryoinjury, which mimics myocardial infarction...

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Autores principales:	Fangjing Xie, Shisan Xu, Yingying Lu, Kin Fung Wong, Lei Sun, Kazi Md Mahmudul Hasan, Alvin C. H. Ma, Gary Tse, Sinai H. C. Manno, Li Tian, Jianbo Yue, Shuk Han Cheng
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/84ea43b53dcc47779a307ebbaf94cfed
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spelling	oai:doaj.org-article:84ea43b53dcc47779a307ebbaf94cfed2021-12-02T16:57:09ZMetformin accelerates zebrafish heart regeneration by inducing autophagy10.1038/s41536-021-00172-w2057-3995https://doaj.org/article/84ea43b53dcc47779a307ebbaf94cfed2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41536-021-00172-whttps://doaj.org/toc/2057-3995Abstract Metformin is one of the most widely used drugs for type 2 diabetes and it also exhibits cardiovascular protective activity. However, the underlying mechanism of its action is not well understood. Here, we used an adult zebrafish model of heart cryoinjury, which mimics myocardial infarction in humans, and demonstrated that autophagy was significantly induced in the injured area. Through a systematic evaluation of the multiple cell types related to cardiac regeneration, we found that metformin enhanced the autophagic flux and improved epicardial, endocardial and vascular endothelial regeneration, accelerated transient collagen deposition and resolution, and induced cardiomyocyte proliferation. Whereas, when the autophagic flux was blocked, then all these processes were delayed. We also showed that metformin transiently enhanced the systolic function of the heart. Taken together, our results indicate that autophagy is positively involved in the metformin-induced acceleration of heart regeneration in zebrafish and suggest that this well-known diabetic drug has clinical value for the prevention and amelioration of myocardial infarction.Fangjing XieShisan XuYingying LuKin Fung WongLei SunKazi Md Mahmudul HasanAlvin C. H. MaGary TseSinai H. C. MannoLi TianJianbo YueShuk Han ChengNature PortfolioarticleMedicineRENnpj Regenerative Medicine, Vol 6, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Fangjing Xie Shisan Xu Yingying Lu Kin Fung Wong Lei Sun Kazi Md Mahmudul Hasan Alvin C. H. Ma Gary Tse Sinai H. C. Manno Li Tian Jianbo Yue Shuk Han Cheng Metformin accelerates zebrafish heart regeneration by inducing autophagy
description	Abstract Metformin is one of the most widely used drugs for type 2 diabetes and it also exhibits cardiovascular protective activity. However, the underlying mechanism of its action is not well understood. Here, we used an adult zebrafish model of heart cryoinjury, which mimics myocardial infarction in humans, and demonstrated that autophagy was significantly induced in the injured area. Through a systematic evaluation of the multiple cell types related to cardiac regeneration, we found that metformin enhanced the autophagic flux and improved epicardial, endocardial and vascular endothelial regeneration, accelerated transient collagen deposition and resolution, and induced cardiomyocyte proliferation. Whereas, when the autophagic flux was blocked, then all these processes were delayed. We also showed that metformin transiently enhanced the systolic function of the heart. Taken together, our results indicate that autophagy is positively involved in the metformin-induced acceleration of heart regeneration in zebrafish and suggest that this well-known diabetic drug has clinical value for the prevention and amelioration of myocardial infarction.
format	article
author	Fangjing Xie Shisan Xu Yingying Lu Kin Fung Wong Lei Sun Kazi Md Mahmudul Hasan Alvin C. H. Ma Gary Tse Sinai H. C. Manno Li Tian Jianbo Yue Shuk Han Cheng
author_facet	Fangjing Xie Shisan Xu Yingying Lu Kin Fung Wong Lei Sun Kazi Md Mahmudul Hasan Alvin C. H. Ma Gary Tse Sinai H. C. Manno Li Tian Jianbo Yue Shuk Han Cheng
author_sort	Fangjing Xie
title	Metformin accelerates zebrafish heart regeneration by inducing autophagy
title_short	Metformin accelerates zebrafish heart regeneration by inducing autophagy
title_full	Metformin accelerates zebrafish heart regeneration by inducing autophagy
title_fullStr	Metformin accelerates zebrafish heart regeneration by inducing autophagy
title_full_unstemmed	Metformin accelerates zebrafish heart regeneration by inducing autophagy
title_sort	metformin accelerates zebrafish heart regeneration by inducing autophagy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/84ea43b53dcc47779a307ebbaf94cfed
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_version_	1718382634512416768

Metformin accelerates zebrafish heart regeneration by inducing autophagy

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