YTHDC1 Mitigates Apoptosis in Bone Marrow Mesenchymal Stem Cells by Inhibiting NfƙBiα and Augmenting Cardiac Function Following Myocardial Infarction.

IF 3.2 4区医学 Q3 CELL & TISSUE ENGINEERING

Cell Transplantation Pub Date : 2024-01-01 DOI:10.1177/09636897241290910

Weiyu Han, Weidong Xiong, Weixing Sun, Weiwei Liu, Yu Zhang, Chaofu Li, Ning Gu, Youcheng Shen, Zhimei Qiu, Chaozhong Li, Yongchao Zhao, Ranzun Zhao

{"title":"YTHDC1 Mitigates Apoptosis in Bone Marrow Mesenchymal Stem Cells by Inhibiting NfƙBiα and Augmenting Cardiac Function Following Myocardial Infarction.","authors":"Weiyu Han, Weidong Xiong, Weixing Sun, Weiwei Liu, Yu Zhang, Chaofu Li, Ning Gu, Youcheng Shen, Zhimei Qiu, Chaozhong Li, Yongchao Zhao, Ranzun Zhao","doi":"10.1177/09636897241290910","DOIUrl":null,"url":null,"abstract":"The therapeutic efficacy of bone marrow mesenchymal stem cells (BMSCs) in myocardial infarction (MI) is hindered by poor cell survival. This study explored the role of N6-methyladenosine (m6A) regulation, specifically YTHDC1, in improving BMSC transplantation for MI. By screening m6A-related regulators in hypoxia and serum deprivation (HSD)-induced BMSC apoptosis, YTHDC1 was found to be downregulated. Overexpression of Ythdc1 in BMSCs reduced apoptosis markers, reactive oxygen species (ROS) release, and improved cell survival under HSD conditions. Conversely, Ythdc1 knockdown enhanced apoptosis. In rat MI models, transplantation of Ythdc1-overexpressing BMSCs improved cardiac function and reduced myocardial fibrosis. Mechanistically, YTHDC1 interacts with nuclear factor kappa B (NF-κB) inhibitor-alpha mRNA, suggesting its involvement in BMSC survival pathways. This study identifies YTHDC1 as a potential target to enhance BMSC efficacy in MI therapy.","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241290910"},"PeriodicalIF":3.2000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528794/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Transplantation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/09636897241290910","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}

引用次数: 0

Abstract

The therapeutic efficacy of bone marrow mesenchymal stem cells (BMSCs) in myocardial infarction (MI) is hindered by poor cell survival. This study explored the role of N6-methyladenosine (m6A) regulation, specifically YTHDC1, in improving BMSC transplantation for MI. By screening m6A-related regulators in hypoxia and serum deprivation (HSD)-induced BMSC apoptosis, YTHDC1 was found to be downregulated. Overexpression of Ythdc1 in BMSCs reduced apoptosis markers, reactive oxygen species (ROS) release, and improved cell survival under HSD conditions. Conversely, Ythdc1 knockdown enhanced apoptosis. In rat MI models, transplantation of Ythdc1-overexpressing BMSCs improved cardiac function and reduced myocardial fibrosis. Mechanistically, YTHDC1 interacts with nuclear factor kappa B (NF-κB) inhibitor-alpha mRNA, suggesting its involvement in BMSC survival pathways. This study identifies YTHDC1 as a potential target to enhance BMSC efficacy in MI therapy.

查看原文本刊更多论文

YTHDC1 通过抑制 NfƙBiα 缓解骨髓间充质干细胞的凋亡并增强心肌梗死后的心功能

骨髓间充质干细胞（BMSCs）在心肌梗死（MI）中的疗效因细胞存活率低而受到阻碍。本研究探讨了N6-甲基腺苷（m6A）调控，特别是YTHDC1在改善骨髓间充质干细胞移植治疗心肌梗死中的作用。通过筛选缺氧和血清剥夺（HSD）诱导的 BMSC 细胞凋亡中与 m6A 相关的调节因子，发现 YTHDC1 被下调。在 BMSCs 中过表达 Ythdc1 可减少细胞凋亡标记物和活性氧（ROS）的释放，并提高细胞在 HSD 条件下的存活率。相反，敲除 Ythdc1 会增强细胞凋亡。在大鼠心肌梗死模型中，移植表达 Ythdc1 的 BMSCs 可改善心脏功能并减少心肌纤维化。从机制上讲，YTHDC1与核因子卡巴B（NF-κB）抑制剂-α mRNA相互作用，表明它参与了BMSC的存活途径。本研究发现 YTHDC1 是提高 BMSC 在心肌梗死治疗中疗效的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell Transplantation 生物-细胞与组织工程

CiteScore

6.00

自引率

3.00%

发文量

审稿时长

6 months

期刊介绍： Cell Transplantation, The Regenerative Medicine Journal is an open access, peer reviewed journal that is published 12 times annually. Cell Transplantation is a multi-disciplinary forum for publication of articles on cell transplantation and its applications to human diseases. Articles focus on a myriad of topics including the physiological, medical, pre-clinical, tissue engineering, stem cell, and device-oriented aspects of the nervous, endocrine, cardiovascular, and endothelial systems, as well as genetically engineered cells. Cell Transplantation also reports on relevant technological advances, clinical studies, and regulatory considerations related to the implantation of cells into the body in order to provide complete coverage of the field.