PARP1 Promotes Heart Regeneration and Cardiomyocyte Proliferation

被引:2
|
作者
Shu, Jiangcheng [1 ,2 ]
Yan, Shu [1 ,2 ]
Ju, Chenhui [1 ,2 ]
Chen, Long [2 ]
Liang, Minglu [2 ]
Wang, Cheng [2 ,3 ,4 ]
Huang, Kai [1 ,2 ,5 ]
机构
[1] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Cardiol, Wuhan, Hubei, Peoples R China
[2] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Clin Ctr Human Genom Res, Wuhan, Hubei, Peoples R China
[3] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Rheumatol, Wuhan, Hubei, Peoples R China
[4] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Rheumatol, 1277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China
[5] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Cardiol, 1277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China
来源
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2024年 / 20卷 / 05期
基金
中国国家自然科学基金;
关键词
cardiomyocyte proliferation; heart regeneration; cell cycle; cell signaling; PARP1; POLY(ADP-RIBOSE) POLYMERASE 1; GENE; PROTECTS; CELLS;
D O I
10.7150/ijbs.85526
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Myocardial infarction causes cardiomyocyte loss, and depleted cardiomyocyte proliferative capacity after birth impinges the heart repair process, eventually leading to heart failure. This study aims to investigate the role of Poly(ADP-Ribose) Polymerase 1 (PARP1) in the regulation of cardiomyocyte proliferation and heart regeneration. Our findings demonstrated that PARP1 knockout impaired cardiomyocyte proliferation, cardiac function, and scar formation, while PARP1 overexpression improved heart regeneration in apical resection -operated mice. Mechanistically, we found that PARP1 interacts with and poly(ADP-ribosyl)ates Heat Shock Protein 90 Alpha Family Class B Member 1 (HSP90AB1) and increases binding between HSP90AB1 and Cell Division Cycle 37 (CDC37) and cell cycle kinase activity, thus activating cardiomyocyte cell cycle. Our results reveal that PARP1 promotes heart regeneration and cardiomyocyte proliferation via poly(ADP-ribosyl)ation of HSP90AB1 activating the cardiomyocyte cell cycle, suggesting that PARP1 may be a potential therapeutic target in treating cardiac injury.
引用
收藏
页码:1602 / 1616
页数:15
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