Serine/Threonine‐Protein Kinase 3 Facilitates Myocardial Repair After Cardiac Injury Possibly Through the Glycogen Synthase Kinase‐3β/β‐Catenin Pathway

Background The neonatal heart maintains its entire regeneration capacity within days after birth. Using quantitative phosphoproteomics technology, we identified that SGK3 (serine/threonine‐protein kinase 3) in the neonatal heart is highly expressed and activated after myocardial infarction. This stu...

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Autores principales:	Ya‐Fei Li, Tian‐Wen Wei, Yi Fan, Tian‐Kai Shan, Jia‐Teng Sun, Bing‐Rui Chen, Zi‐Mu Wang, Ling‐Feng Gu, Tong‐Tong Yang, Liu Liu, Chong Du, Yao Ma, Hao Wang, Rui Sun, Yong‐Yue Wei, Feng Chen, Xue‐Jiang Guo, Xiang‐Qing Kong, Lian‐Sheng Wang
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	cardiac protection cardiomyocyte proliferation myocardial infarction SGK3 Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/e236d05ae2424756a3d0564dfbf06d95
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spelling	oai:doaj.org-article:e236d05ae2424756a3d0564dfbf06d952021-11-16T10:22:43ZSerine/Threonine‐Protein Kinase 3 Facilitates Myocardial Repair After Cardiac Injury Possibly Through the Glycogen Synthase Kinase‐3β/β‐Catenin Pathway10.1161/JAHA.121.0228022047-9980https://doaj.org/article/e236d05ae2424756a3d0564dfbf06d952021-11-01T00:00:00Zhttps://www.ahajournals.org/doi/10.1161/JAHA.121.022802https://doaj.org/toc/2047-9980Background The neonatal heart maintains its entire regeneration capacity within days after birth. Using quantitative phosphoproteomics technology, we identified that SGK3 (serine/threonine‐protein kinase 3) in the neonatal heart is highly expressed and activated after myocardial infarction. This study aimed to uncover the function and related mechanisms of SGK3 on cardiomyocyte proliferation and cardiac repair after apical resection or ischemia/reperfusion injury. Methods and Results The effect of SGK3 on proliferation and oxygen glucose deprivation/reoxygenation– induced apoptosis in isolated cardiomyocytes was evaluated using cardiomyocyte‐specific SGK3 overexpression or knockdown adenovirus5 vector. In vivo, gain‐ and loss‐of‐function experiments using cardiomyocyte‐specific adeno‐associated virus 9 were performed to determine the effect of SGK3 in cardiomyocyte proliferation and cardiac repair after apical resection or ischemia/reperfusion injury. In vitro, overexpression of SGK3 enhanced, whereas knockdown of SGK3 decreased, the cardiomyocyte proliferation ratio. In vivo, inhibiting the expression of SGK3 shortened the time window of cardiac regeneration after apical resection in neonatal mice, and overexpression of SGK3 significantly promoted myocardial repair and cardiac function recovery after ischemia/reperfusion injury in adult mice. Mechanistically, SGK3 promoted cardiomyocyte regeneration and myocardial repair after cardiac injury by inhibiting GSK‐3β (glycogen synthase kinase‐3β) activity and upregulating β‐catenin expression. SGK3 also upregulated the expression of cell cycle promoting genes G1/S‐specific cyclin‐D1, c‐myc (cellular‐myelocytomatosis viral oncogene), and cdc20 (cell division cycle 20), but downregulated the expression of cell cycle negative regulators cyclin kinase inhibitor P 21 and cyclin kinase inhibitor P 27. Conclusions Our study reveals a key role of SGK3 on cardiac repair after apical resection or ischemia/reperfusion injury, which may reopen a novel therapeutic option for myocardial infarction.Ya‐Fei LiTian‐Wen WeiYi FanTian‐Kai ShanJia‐Teng SunBing‐Rui ChenZi‐Mu WangLing‐Feng GuTong‐Tong YangLiu LiuChong DuYao MaHao WangRui SunYong‐Yue WeiFeng ChenXue‐Jiang GuoXiang‐Qing KongLian‐Sheng WangWileyarticlecardiac protectioncardiomyocyte proliferationmyocardial infarctionSGK3Diseases of the circulatory (Cardiovascular) systemRC666-701ENJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 10, Iss 22 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cardiac protection cardiomyocyte proliferation myocardial infarction SGK3 Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	cardiac protection cardiomyocyte proliferation myocardial infarction SGK3 Diseases of the circulatory (Cardiovascular) system RC666-701 Ya‐Fei Li Tian‐Wen Wei Yi Fan Tian‐Kai Shan Jia‐Teng Sun Bing‐Rui Chen Zi‐Mu Wang Ling‐Feng Gu Tong‐Tong Yang Liu Liu Chong Du Yao Ma Hao Wang Rui Sun Yong‐Yue Wei Feng Chen Xue‐Jiang Guo Xiang‐Qing Kong Lian‐Sheng Wang Serine/Threonine‐Protein Kinase 3 Facilitates Myocardial Repair After Cardiac Injury Possibly Through the Glycogen Synthase Kinase‐3β/β‐Catenin Pathway
description	Background The neonatal heart maintains its entire regeneration capacity within days after birth. Using quantitative phosphoproteomics technology, we identified that SGK3 (serine/threonine‐protein kinase 3) in the neonatal heart is highly expressed and activated after myocardial infarction. This study aimed to uncover the function and related mechanisms of SGK3 on cardiomyocyte proliferation and cardiac repair after apical resection or ischemia/reperfusion injury. Methods and Results The effect of SGK3 on proliferation and oxygen glucose deprivation/reoxygenation– induced apoptosis in isolated cardiomyocytes was evaluated using cardiomyocyte‐specific SGK3 overexpression or knockdown adenovirus5 vector. In vivo, gain‐ and loss‐of‐function experiments using cardiomyocyte‐specific adeno‐associated virus 9 were performed to determine the effect of SGK3 in cardiomyocyte proliferation and cardiac repair after apical resection or ischemia/reperfusion injury. In vitro, overexpression of SGK3 enhanced, whereas knockdown of SGK3 decreased, the cardiomyocyte proliferation ratio. In vivo, inhibiting the expression of SGK3 shortened the time window of cardiac regeneration after apical resection in neonatal mice, and overexpression of SGK3 significantly promoted myocardial repair and cardiac function recovery after ischemia/reperfusion injury in adult mice. Mechanistically, SGK3 promoted cardiomyocyte regeneration and myocardial repair after cardiac injury by inhibiting GSK‐3β (glycogen synthase kinase‐3β) activity and upregulating β‐catenin expression. SGK3 also upregulated the expression of cell cycle promoting genes G1/S‐specific cyclin‐D1, c‐myc (cellular‐myelocytomatosis viral oncogene), and cdc20 (cell division cycle 20), but downregulated the expression of cell cycle negative regulators cyclin kinase inhibitor P 21 and cyclin kinase inhibitor P 27. Conclusions Our study reveals a key role of SGK3 on cardiac repair after apical resection or ischemia/reperfusion injury, which may reopen a novel therapeutic option for myocardial infarction.
format	article
author	Ya‐Fei Li Tian‐Wen Wei Yi Fan Tian‐Kai Shan Jia‐Teng Sun Bing‐Rui Chen Zi‐Mu Wang Ling‐Feng Gu Tong‐Tong Yang Liu Liu Chong Du Yao Ma Hao Wang Rui Sun Yong‐Yue Wei Feng Chen Xue‐Jiang Guo Xiang‐Qing Kong Lian‐Sheng Wang
author_facet	Ya‐Fei Li Tian‐Wen Wei Yi Fan Tian‐Kai Shan Jia‐Teng Sun Bing‐Rui Chen Zi‐Mu Wang Ling‐Feng Gu Tong‐Tong Yang Liu Liu Chong Du Yao Ma Hao Wang Rui Sun Yong‐Yue Wei Feng Chen Xue‐Jiang Guo Xiang‐Qing Kong Lian‐Sheng Wang
author_sort	Ya‐Fei Li
title	Serine/Threonine‐Protein Kinase 3 Facilitates Myocardial Repair After Cardiac Injury Possibly Through the Glycogen Synthase Kinase‐3β/β‐Catenin Pathway
title_short	Serine/Threonine‐Protein Kinase 3 Facilitates Myocardial Repair After Cardiac Injury Possibly Through the Glycogen Synthase Kinase‐3β/β‐Catenin Pathway
title_full	Serine/Threonine‐Protein Kinase 3 Facilitates Myocardial Repair After Cardiac Injury Possibly Through the Glycogen Synthase Kinase‐3β/β‐Catenin Pathway
title_fullStr	Serine/Threonine‐Protein Kinase 3 Facilitates Myocardial Repair After Cardiac Injury Possibly Through the Glycogen Synthase Kinase‐3β/β‐Catenin Pathway
title_full_unstemmed	Serine/Threonine‐Protein Kinase 3 Facilitates Myocardial Repair After Cardiac Injury Possibly Through the Glycogen Synthase Kinase‐3β/β‐Catenin Pathway
title_sort	serine/threonine‐protein kinase 3 facilitates myocardial repair after cardiac injury possibly through the glycogen synthase kinase‐3β/β‐catenin pathway
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/e236d05ae2424756a3d0564dfbf06d95
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Serine/Threonine‐Protein Kinase 3 Facilitates Myocardial Repair After Cardiac Injury Possibly Through the Glycogen Synthase Kinase‐3β/β‐Catenin Pathway

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