Fosl1 is vital to heart regeneration upon apex resection in adult Xenopus tropicalis

Abstract Cardiovascular disease is the leading cause of death in the world due to losing regenerative capacity in the adult heart. Frogs possess remarkable capacities to regenerate multiple organs, including spinal cord, tail, and limb, but the response to heart injury and the underlying molecular m...

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Autores principales:	Hai-Yan Wu, Yi-Min Zhou, Zhu-Qin Liao, Jia-Wen Zhong, You-Bin Liu, Hui Zhao, Chi-Qian Liang, Rui-Jin Huang, Kyu-Sang Park, Shan-Shan Feng, Li Zheng, Dong-Qing Cai, Xu-Feng Qi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/8add434833e94dcf9165b3d055719b10
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spelling	oai:doaj.org-article:8add434833e94dcf9165b3d055719b102021-12-02T16:10:53ZFosl1 is vital to heart regeneration upon apex resection in adult Xenopus tropicalis10.1038/s41536-021-00146-y2057-3995https://doaj.org/article/8add434833e94dcf9165b3d055719b102021-06-01T00:00:00Zhttps://doi.org/10.1038/s41536-021-00146-yhttps://doaj.org/toc/2057-3995Abstract Cardiovascular disease is the leading cause of death in the world due to losing regenerative capacity in the adult heart. Frogs possess remarkable capacities to regenerate multiple organs, including spinal cord, tail, and limb, but the response to heart injury and the underlying molecular mechanism remains largely unclear. Here we demonstrated that cardiomyocyte proliferation greatly contributes to heart regeneration in adult X. tropicalis upon apex resection. Using RNA-seq and qPCR, we found that the expression of Fos-like antigen 1 (Fosl1) was dramatically upregulated in early stage of heart injury. To study Fosl1 function in heart regeneration, its expression was modulated in vitro and in vivo. Overexpression of X. tropicalis Fosl1 significantly promoted the proliferation of cardiomyocyte cell line H9c2. Consistently, endogenous Fosl1 knockdown suppressed the proliferation of H9c2 cells and primary cardiomyocytes isolated from neonatal mice. Taking use of a cardiomyocyte-specific dominant-negative approach, we show that blocking Fosl1 function leads to defects in cardiomyocyte proliferation during X. tropicalis heart regeneration. We further show that knockdown of Fosl1 can suppress the capacity of heart regeneration in neonatal mice, but overexpression of Fosl1 can improve the cardiac function in adult mouse upon myocardium infarction. Co-immunoprecipitation, luciferase reporter, and ChIP analysis reveal that Fosl1 interacts with JunB and promotes the expression of Cyclin-T1 (Ccnt1) during heart regeneration. In conclusion, we demonstrated that Fosl1 plays an essential role in cardiomyocyte proliferation and heart regeneration in vertebrates, at least in part, through interaction with JunB, thereby promoting expression of cell cycle regulators including Ccnt1.Hai-Yan WuYi-Min ZhouZhu-Qin LiaoJia-Wen ZhongYou-Bin LiuHui ZhaoChi-Qian LiangRui-Jin HuangKyu-Sang ParkShan-Shan FengLi ZhengDong-Qing CaiXu-Feng QiNature PortfolioarticleMedicineRENnpj Regenerative Medicine, Vol 6, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Hai-Yan Wu Yi-Min Zhou Zhu-Qin Liao Jia-Wen Zhong You-Bin Liu Hui Zhao Chi-Qian Liang Rui-Jin Huang Kyu-Sang Park Shan-Shan Feng Li Zheng Dong-Qing Cai Xu-Feng Qi Fosl1 is vital to heart regeneration upon apex resection in adult Xenopus tropicalis
description	Abstract Cardiovascular disease is the leading cause of death in the world due to losing regenerative capacity in the adult heart. Frogs possess remarkable capacities to regenerate multiple organs, including spinal cord, tail, and limb, but the response to heart injury and the underlying molecular mechanism remains largely unclear. Here we demonstrated that cardiomyocyte proliferation greatly contributes to heart regeneration in adult X. tropicalis upon apex resection. Using RNA-seq and qPCR, we found that the expression of Fos-like antigen 1 (Fosl1) was dramatically upregulated in early stage of heart injury. To study Fosl1 function in heart regeneration, its expression was modulated in vitro and in vivo. Overexpression of X. tropicalis Fosl1 significantly promoted the proliferation of cardiomyocyte cell line H9c2. Consistently, endogenous Fosl1 knockdown suppressed the proliferation of H9c2 cells and primary cardiomyocytes isolated from neonatal mice. Taking use of a cardiomyocyte-specific dominant-negative approach, we show that blocking Fosl1 function leads to defects in cardiomyocyte proliferation during X. tropicalis heart regeneration. We further show that knockdown of Fosl1 can suppress the capacity of heart regeneration in neonatal mice, but overexpression of Fosl1 can improve the cardiac function in adult mouse upon myocardium infarction. Co-immunoprecipitation, luciferase reporter, and ChIP analysis reveal that Fosl1 interacts with JunB and promotes the expression of Cyclin-T1 (Ccnt1) during heart regeneration. In conclusion, we demonstrated that Fosl1 plays an essential role in cardiomyocyte proliferation and heart regeneration in vertebrates, at least in part, through interaction with JunB, thereby promoting expression of cell cycle regulators including Ccnt1.
format	article
author	Hai-Yan Wu Yi-Min Zhou Zhu-Qin Liao Jia-Wen Zhong You-Bin Liu Hui Zhao Chi-Qian Liang Rui-Jin Huang Kyu-Sang Park Shan-Shan Feng Li Zheng Dong-Qing Cai Xu-Feng Qi
author_facet	Hai-Yan Wu Yi-Min Zhou Zhu-Qin Liao Jia-Wen Zhong You-Bin Liu Hui Zhao Chi-Qian Liang Rui-Jin Huang Kyu-Sang Park Shan-Shan Feng Li Zheng Dong-Qing Cai Xu-Feng Qi
author_sort	Hai-Yan Wu
title	Fosl1 is vital to heart regeneration upon apex resection in adult Xenopus tropicalis
title_short	Fosl1 is vital to heart regeneration upon apex resection in adult Xenopus tropicalis
title_full	Fosl1 is vital to heart regeneration upon apex resection in adult Xenopus tropicalis
title_fullStr	Fosl1 is vital to heart regeneration upon apex resection in adult Xenopus tropicalis
title_full_unstemmed	Fosl1 is vital to heart regeneration upon apex resection in adult Xenopus tropicalis
title_sort	fosl1 is vital to heart regeneration upon apex resection in adult xenopus tropicalis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8add434833e94dcf9165b3d055719b10
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Fosl1 is vital to heart regeneration upon apex resection in adult Xenopus tropicalis

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