Research Paper Volume 11, Issue 24 pp 12546—12567

Sirt1-inducible deacetylation of p21 promotes cardiomyocyte proliferation

Bing Li1,2,3, , Mengsha Li1, , Xinzhong Li1,3, , Hairui Li1, , Yanxian Lai1, , Senlin Huang1,3, , Xiang He1,3, , Xiaoyun Si1, , Hao Zheng1,3, , Wangjun Liao4, , Yulin Liao1,3, , Jianping Bin1,3, ,

  • 1 Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
  • 2 School of Medicine, Guizhou University, Guiyang, Guizhou 550025, China
  • 3 Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510005, China
  • 4 Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

Received: September 10, 2019       Accepted: November 26, 2019       Published: December 26, 2019
How to Cite

Copyright © 2019 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Inducing cardiomyocyte proliferation is a hopeful approach for cardiac regeneration following myocardial infarction. Previous studies have shown that p21 inhibits the cardiomyocyte proliferation and cardiac regeneration. Deacetylation of p21 by Sirt1 deacetylase may reduce p21 abundance and remove p21-induced cell cycle arrest. However, whether p21 deacetylation and Sirt1 deacetylate control cardiomyocyte proliferation is unclear. Here, we show that acetylation of p21 induces cardiomyocyte proliferation arrest, whereas blocking the acetylation of p21 increases cardiomyocyte proliferation. P21 can be acetylated by Sirt1, and Sirt1 activate p21 ubiquitination through deacetylation. Additionally, overexpression of Sirt1 induces EdU-, pH3-, and Aurora B-positive cardiomyocytes in neonatal and adult mice. In contrast, depletion of Sirt1 reduces cardiomyocyte proliferation in vitro and in vivo. Moreover, Sirt1 protects cardiac function, reduces cardiac remodeling, inhibits cardiomyocyte apoptosis, and attenuates cardiomyocyte hypertrophy post-myocardial infarction. These results suggest that Sirt1-induced p21 deacetylation plays an essential role in cardiomyocyte proliferation and that it could be a novel therapeutic strategy for myocardial infarction.


AAV9: adeno-associated virus serotype 9; AdV: adenovirus; CMs: cardiomyocytes; EdU: 5-ethynyl-2′-deoxyuridine; GEO: Gene expression omnibus; HDACs: histone deacetylases; LAD: left anterior descending; LSD: least significant difference; LVEDd: left ventricular end-diastolic diameter; LVEF: left ventricular ejection fraction; LVESd: left ventricular end-systolic diameter; LVFS: left ventricular fractional shortening; MI: myocardial infarction; NC: negative control; P1: post-natal day 1; P6: post-natal day 6; P28: post-natal day 28; pH3: histone H3 phosphorylated at serine10; siRNA: small interfering RNA; Sirt1: Sirtuin1; WGA: wheat germ agglutinin.