KLF5调控骨髓干细胞外泌体来源的miR-152-3p改善心肌梗死后室性心律失常

IF 3.3 3区 医学 Q2 CELL & TISSUE ENGINEERING
Stem Cells International Pub Date : 2025-08-09 eCollection Date: 2025-01-01 DOI:10.1155/sci/5572221
Chen Wu, Xin-Yue Zou, Yi-Wen Jiang, Da-Wei Lin, Feng Jiang, Yao-Sheng Wang
{"title":"KLF5调控骨髓干细胞外泌体来源的miR-152-3p改善心肌梗死后室性心律失常","authors":"Chen Wu, Xin-Yue Zou, Yi-Wen Jiang, Da-Wei Lin, Feng Jiang, Yao-Sheng Wang","doi":"10.1155/sci/5572221","DOIUrl":null,"url":null,"abstract":"<p><p>Cardiac fibroblasts (CFs) are activated into cardiac myofibroblasts (CMFs) in myocardial infarction (MI) and promote fibrosis, playing a crucial role in deteriorating cardiac function and inducing fatal arrhythmias. Transplantation of bone marrow mesenchymal stem cells (BMSCs) has emerged as a promising therapeutic approach for ischemic heart diseases, including MI. Recent studies have indicated that BMSCs can modulate the survival, differentiation, and antifibrotic activity of CFs. Kruppel-like factor 5 (KLF5) is a significant transcription factor involved in maintaining stem cell properties. In this study, we aimed to investigate whether overexpression of KLF5 could enhance the cardioprotective characteristics of BMSCs, particularly in terms of mitigating structural and electrical remodeling. Our in vivo experiments revealed that transplantation of KLF5-overexpressing BMSCs in mice with MI led to a substantial reduction in ventricular fibrosis and the occurrence of ventricular arrhythmias (VAs). In vitro coculture experiments demonstrated that BMSCs could inhibit CFs activation and cytoskeleton protein bundling induced by hypoxia through paracrine effects, resulting in reduced expression of α-SMA and Collagen I. Furthermore, coculturing BMSCs significantly reduced the expression of connexin 43, alleviated hypoxia, increased the expression of inward-rectifier K<sup>+</sup> current (Kir), and decreased voltage-dependent K<sup>+</sup> (Kv) currents. Mechanistically, KLF5 enhanced the effects of BMSCs by facilitating the transfer of miR-152-3 p from BMSCs-derived exosomes to CFs. Overall, our findings show that BMSCs transplantation promotes the recovery of cardiac function and reduces the incidence of arrhythmias by inhibiting CFs activation and modulating CFs Kir current remodeling. Additionally, overexpression of KLF5 enhances the cardioprotective effects of BMSCs.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"5572221"},"PeriodicalIF":3.3000,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357777/pdf/","citationCount":"0","resultStr":"{\"title\":\"KLF5 Regulation of Exosome-Derived miR-152-3p From Bone Marrow Stem Cells Improves Ventricular Arrhythmia After Myocardial Infarction.\",\"authors\":\"Chen Wu, Xin-Yue Zou, Yi-Wen Jiang, Da-Wei Lin, Feng Jiang, Yao-Sheng Wang\",\"doi\":\"10.1155/sci/5572221\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cardiac fibroblasts (CFs) are activated into cardiac myofibroblasts (CMFs) in myocardial infarction (MI) and promote fibrosis, playing a crucial role in deteriorating cardiac function and inducing fatal arrhythmias. Transplantation of bone marrow mesenchymal stem cells (BMSCs) has emerged as a promising therapeutic approach for ischemic heart diseases, including MI. Recent studies have indicated that BMSCs can modulate the survival, differentiation, and antifibrotic activity of CFs. Kruppel-like factor 5 (KLF5) is a significant transcription factor involved in maintaining stem cell properties. In this study, we aimed to investigate whether overexpression of KLF5 could enhance the cardioprotective characteristics of BMSCs, particularly in terms of mitigating structural and electrical remodeling. Our in vivo experiments revealed that transplantation of KLF5-overexpressing BMSCs in mice with MI led to a substantial reduction in ventricular fibrosis and the occurrence of ventricular arrhythmias (VAs). In vitro coculture experiments demonstrated that BMSCs could inhibit CFs activation and cytoskeleton protein bundling induced by hypoxia through paracrine effects, resulting in reduced expression of α-SMA and Collagen I. Furthermore, coculturing BMSCs significantly reduced the expression of connexin 43, alleviated hypoxia, increased the expression of inward-rectifier K<sup>+</sup> current (Kir), and decreased voltage-dependent K<sup>+</sup> (Kv) currents. Mechanistically, KLF5 enhanced the effects of BMSCs by facilitating the transfer of miR-152-3 p from BMSCs-derived exosomes to CFs. Overall, our findings show that BMSCs transplantation promotes the recovery of cardiac function and reduces the incidence of arrhythmias by inhibiting CFs activation and modulating CFs Kir current remodeling. Additionally, overexpression of KLF5 enhances the cardioprotective effects of BMSCs.</p>\",\"PeriodicalId\":21962,\"journal\":{\"name\":\"Stem Cells International\",\"volume\":\"2025 \",\"pages\":\"5572221\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-08-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357777/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Stem Cells International\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1155/sci/5572221\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stem Cells International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/sci/5572221","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
引用次数: 0

摘要

心肌成纤维细胞(CFs)在心肌梗死(MI)中被激活成心肌成纤维细胞(CMFs)并促进纤维化,在心功能恶化和致死性心律失常中起着至关重要的作用。骨髓间充质干细胞(BMSCs)移植已成为缺血性心脏病(包括心肌梗死)的一种有前景的治疗方法。最近的研究表明,骨髓间充质干细胞可以调节CFs的存活、分化和抗纤维化活性。kruppel样因子5 (KLF5)是一个重要的转录因子,参与维持干细胞的特性。在这项研究中,我们旨在研究KLF5的过表达是否可以增强骨髓间充质干细胞的心脏保护特性,特别是在减轻结构和电重构方面。我们的体内实验显示,在心肌梗死小鼠中移植过表达klf5的骨髓间充质干细胞可显著减少心室纤维化和室性心律失常(VAs)的发生。体外共培养实验表明,骨髓间充质干细胞可通过旁分泌作用抑制缺氧诱导的CFs活化和细胞骨架蛋白捆绑,导致α-SMA和胶原i的表达降低。此外,骨髓间充质干细胞共培养可显著降低连接蛋白43的表达,缓解缺氧,增加内向流K+电流(Kir)的表达,降低电压依赖性K+电流(Kv)。在机制上,KLF5通过促进miR-152-3 p从BMSCs来源的外泌体转移到CFs来增强BMSCs的作用。总的来说,我们的研究结果表明,骨髓间充质干细胞移植通过抑制CFs激活和调节CFs Kir电流重塑来促进心功能的恢复,减少心律失常的发生率。此外,KLF5的过表达增强了骨髓间充质干细胞的心脏保护作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
KLF5 Regulation of Exosome-Derived miR-152-3p From Bone Marrow Stem Cells Improves Ventricular Arrhythmia After Myocardial Infarction.

Cardiac fibroblasts (CFs) are activated into cardiac myofibroblasts (CMFs) in myocardial infarction (MI) and promote fibrosis, playing a crucial role in deteriorating cardiac function and inducing fatal arrhythmias. Transplantation of bone marrow mesenchymal stem cells (BMSCs) has emerged as a promising therapeutic approach for ischemic heart diseases, including MI. Recent studies have indicated that BMSCs can modulate the survival, differentiation, and antifibrotic activity of CFs. Kruppel-like factor 5 (KLF5) is a significant transcription factor involved in maintaining stem cell properties. In this study, we aimed to investigate whether overexpression of KLF5 could enhance the cardioprotective characteristics of BMSCs, particularly in terms of mitigating structural and electrical remodeling. Our in vivo experiments revealed that transplantation of KLF5-overexpressing BMSCs in mice with MI led to a substantial reduction in ventricular fibrosis and the occurrence of ventricular arrhythmias (VAs). In vitro coculture experiments demonstrated that BMSCs could inhibit CFs activation and cytoskeleton protein bundling induced by hypoxia through paracrine effects, resulting in reduced expression of α-SMA and Collagen I. Furthermore, coculturing BMSCs significantly reduced the expression of connexin 43, alleviated hypoxia, increased the expression of inward-rectifier K+ current (Kir), and decreased voltage-dependent K+ (Kv) currents. Mechanistically, KLF5 enhanced the effects of BMSCs by facilitating the transfer of miR-152-3 p from BMSCs-derived exosomes to CFs. Overall, our findings show that BMSCs transplantation promotes the recovery of cardiac function and reduces the incidence of arrhythmias by inhibiting CFs activation and modulating CFs Kir current remodeling. Additionally, overexpression of KLF5 enhances the cardioprotective effects of BMSCs.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Stem Cells International
Stem Cells International CELL & TISSUE ENGINEERING-
CiteScore
8.10
自引率
2.30%
发文量
188
审稿时长
18 weeks
期刊介绍: Stem Cells International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies in all areas of stem cell biology and applications. The journal will consider basic, translational, and clinical research, including animal models and clinical trials. Topics covered include, but are not limited to: embryonic stem cells; induced pluripotent stem cells; tissue-specific stem cells; stem cell differentiation; genetics and epigenetics; cancer stem cells; stem cell technologies; ethical, legal, and social issues.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信