The longevity protein p66Shc is required for neonatal heart regeneration

Chengzhen Huang; Tong Ding; Yuan Zhang; Xunkai Li; Xin Sun; Shuangjie Lv; Yanyan Hao; Lina Bai; Ning Liu; Yifan Xie; Houzao Chen; Yu Nie

doi:10.1016/j.yjmcc.2023.02.004

The longevity protein p66^Shc is required for neonatal heart regeneration

J Mol Cell Cardiol. 2023 Apr:177:21-27. doi: 10.1016/j.yjmcc.2023.02.004. Epub 2023 Feb 22.

Authors

Chengzhen Huang¹, Tong Ding², Yuan Zhang³, Xunkai Li⁴, Xin Sun⁴, Shuangjie Lv⁴, Yanyan Hao⁵, Lina Bai⁶, Ning Liu⁶, Yifan Xie⁶, Houzao Chen⁷, Yu Nie⁸

Affiliations

¹ State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, PR China; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
² State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China; Department of Cardiac Surgery, Peking University Third Hospital, 49 N Garden Rd, Haidian District, Beijing 100191, PR China.
³ National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine, Fuwai Central-China Hospital, Central China Branch of National Center for Cardiovascular Diseases, Zhengzhou University, Zhengzhou, 450046, China.
⁴ State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, PR China.
⁵ Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan 030001, China.
⁶ State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
⁷ State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, PR China. Electronic address: chenhouzao@ibms.cams.cn.
⁸ State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China; National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine, Fuwai Central-China Hospital, Central China Branch of National Center for Cardiovascular Diseases, Zhengzhou University, Zhengzhou, 450046, China. Electronic address: nieyu@fuwaihospital.org.

PMID: 36827872
DOI: 10.1016/j.yjmcc.2023.02.004

Abstract

The longevity protein p66^Shc is essential for the senescence signaling that is involved in heart regeneration and remodeling. However, the exact role of p66^Shc in heart regeneration is unknown. In this study, we found that p66^Shc deficiency decreased neonatal mouse cardiomyocyte (CM) proliferation and impeded neonatal heart regeneration after apical resection injury. RNA sequencing and functional verification demonstrated that p66^Shc regulated CM proliferation by activating β-catenin signaling. These findings reveal the critical role of p66^Shc in neonatal heart regeneration and provide new insights into senescence signaling in heart regeneration.

Keywords: Cardiomyocyte proliferation; Heart regeneration; p66(Shc); β-Catenin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Mice
Phosphorylation
Shc Signaling Adaptor Proteins / genetics
Shc Signaling Adaptor Proteins / metabolism
Signal Transduction*
Src Homology 2 Domain-Containing, Transforming Protein 1 / genetics
Src Homology 2 Domain-Containing, Transforming Protein 1 / metabolism

Substances

Shc Signaling Adaptor Proteins
Src Homology 2 Domain-Containing, Transforming Protein 1