Metformin accelerates zebrafish heart regeneration by inducing autophagy.

Autor:	Xie F; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China., Xu S; School of Life Sciences, Guangxi Normal University, Guilin, China.; Guangxi Universities Key Laboratory of Stem Cell and Biopharmaceutical Technology, Guangxi Normal University, Guilin, China., Lu Y; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.; City University of Hong Kong Shenzhen Research Institute, Shenzhen, China., Wong KF; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong, China., Sun L; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong, China., Hasan KMM; Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, China., Ma ACH; Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, China., Tse G; Kent and Medway Medical School, Canterbury, UK., Manno SHC; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China., Tian L; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China., Yue J; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China. jianbyue@cityu.edu.hk.; City University of Hong Kong Shenzhen Research Institute, Shenzhen, China. jianbyue@cityu.edu.hk., Cheng SH; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China. bhcheng@cityu.edu.hk.
Jazyk:	angličtina
Zdroj:	NPJ Regenerative medicine [NPJ Regen Med] 2021 Oct 08; Vol. 6 (1), pp. 62. Date of Electronic Publication: 2021 Oct 08.
DOI:	10.1038/s41536-021-00172-w
Abstrakt:	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. (© 2021. The Author(s).)
Databáze:	MEDLINE
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