Chong Du , Shan Zhao , Tiankai Shan , Xudong Han , Qiqi Jiang , Jiawen Chen , Lingfeng Gu , Tianwen Wei , Tongtong Yang , Sibo Wang , Hao Wang , Xuejiang Guo , Liansheng Wang
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CNBP is highly expressed within 7 days post-birth while decreases significantly with the loss of regenerative ability. <em>In vitro</em>, overexpression of CNBP promoted CM proliferation and survival, whereas knockdown of CNBP inhibited these processes. <em>In vivo</em>, 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.</p></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"189 ","pages":"Pages 66-82"},"PeriodicalIF":4.9000,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cellular nucleic acid binding protein facilitates cardiac repair after myocardial infarction by activating β-catenin signaling\",\"authors\":\"Chong Du , Shan Zhao , Tiankai Shan , Xudong Han , Qiqi Jiang , Jiawen Chen , Lingfeng Gu , Tianwen Wei , Tongtong Yang , Sibo Wang , Hao Wang , Xuejiang Guo , Liansheng Wang\",\"doi\":\"10.1016/j.yjmcc.2024.02.008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The regenerative capacity of the adult mammalian heart is limited, while the neonatal heart is an organ with regenerative and proliferative ability. 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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.</p></div>\",\"PeriodicalId\":16402,\"journal\":{\"name\":\"Journal of molecular and cellular cardiology\",\"volume\":\"189 \",\"pages\":\"Pages 66-82\"},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2024-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of molecular and cellular cardiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0022282824000336\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of molecular and cellular cardiology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0022282824000336","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
摘要
成年哺乳动物心脏的再生能力有限,而新生儿心脏是一个具有再生和增殖能力的器官。激活成体心肌细胞(CMs)重新进入细胞周期是治疗心肌梗死(MI)和心力衰竭等缺血性心脏病的有效方法。在此,我们旨在揭示细胞核酸结合蛋白(CNBP)在心脏损伤后心脏再生和修复中的作用和潜在机制。CNBP在出生后7天内高表达,随着再生能力的丧失而显著降低。在体外,过表达 CNBP 可促进 CM 的增殖和存活,而敲除 CNBP 则会抑制这些过程。在体内,敲除新生小鼠心尖切除后 CM 中的 CNBP 会严重阻碍心肌再生。在成年心肌梗死小鼠中,心肌梗死边界区的CM特异性CNBP过表达可改善急性期的心肌损伤,并在长期内促进CM增殖和功能恢复。TMT标记的定量蛋白质组分析表明,CNBP过表达可促进DNA复制、细胞周期进展和细胞分裂。此外,荧光素酶报告和染色质免疫沉淀(ChIP)分析表明,CNBP能直接与β-catenin启动子结合并促进其转录。CNBP 还能上调 G1/S 细胞周期相关基因 CCNE1、CDK2 和 CDK4 的表达。总之,我们的研究揭示了 CNBP 在促进损伤后心脏修复中的积极作用,为治疗心肌梗死提供了新的治疗方案。
Cellular nucleic acid binding protein facilitates cardiac repair after myocardial infarction by activating β-catenin signaling
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.
期刊介绍:
The Journal of Molecular and Cellular Cardiology publishes work advancing knowledge of the mechanisms responsible for both normal and diseased cardiovascular function. To this end papers are published in all relevant areas. These include (but are not limited to): structural biology; genetics; proteomics; morphology; stem cells; molecular biology; metabolism; biophysics; bioengineering; computational modeling and systems analysis; electrophysiology; pharmacology and physiology. Papers are encouraged with both basic and translational approaches. The journal is directed not only to basic scientists but also to clinical cardiologists who wish to follow the rapidly advancing frontiers of basic knowledge of the heart and circulation.