1. Cellular nucleic acid binding protein facilitates cardiac repair after myocardial infarction by activating β-catenin signaling.
- Author
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Du, Chong, Zhao, Shan, Shan, Tiankai, Han, Xudong, Jiang, Qiqi, Chen, Jiawen, Gu, Lingfeng, Wei, Tianwen, Yang, Tongtong, Wang, Sibo, Wang, Hao, Guo, Xuejiang, and Wang, Liansheng
- Subjects
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CARDIAC regeneration , *NUCLEIC acids , *MYOCARDIAL infarction , *CARRIER proteins , *CATENINS , *CORONARY disease , *MYOCARDIAL ischemia - Abstract
The regenerative capacity of the adult mammalian heart is limited, while the neonatal heart is an organ with regenerative and proliferative ability. Activating adult cardiomyocytes (CMs) to re-enter the cell cycle is an effective therapeutic method for ischemic heart disease such as myocardial infarction (MI) and heart failure. Here, we aimed to reveal the role and potential mechanisms of cellular nucleic acid binding protein (CNBP) in cardiac regeneration and repair after heart injury. CNBP is highly expressed within 7 days post-birth while decreases significantly with the loss of regenerative ability. In vitro , overexpression of CNBP promoted CM proliferation and survival, whereas knockdown of CNBP inhibited these processes. In vivo , knockdown of CNBP in CMs robustly hindered myocardial regeneration after apical resection in neonatal mice. In adult MI mice, CM-specific CNBP overexpression in the infarct border zone ameliorated myocardial injury in acute stage and facilitated CM proliferation and functional recovery in the long term. Quantitative proteomic analysis with TMT labeling showed that CNBP overexpression promoted the DNA replication, cell cycle progression, and cell division. Mechanically, CNBP overexpression increased the expression of β-catenin and its downstream target genes CCND1 and c-myc; Furthermore, Luciferase reporter and Chromatin immunoprecipitation (ChIP) assays showed that CNBP could directly bind to the β-catenin promoter and promote its transcription. CNBP also upregulated the expression of G1/S-related cell cycle genes CCNE1, CDK2, and CDK4. Collectively, our study reveals the positive role of CNBP in promoting cardiac repair after injury, providing a new therapeutic option for the treatment of MI. [Display omitted] • CNBP is highly expressed in neonatal hearts while decreases significantly in adults with the loss of regenerative ability. • CNBP overexpression can facilitate cardiac repair by promoting cardiomyocyte CM proliferation and survival. • β-catenin plays an important role in the process of CNBP promoting cardiac regeneration. • CNBP can directly bind to the β-catenin promoter, activate the expression of β-catenin and its downstream genes in CMs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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