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

被引：1

作者：

Han, Weiyu ^{[1
]}

Xiong, Weidong ^{[1
]}

Sun, Weixing ^{[1
,2
]}

Liu, Weiwei ^{[1
]}

Zhang, Yu ^{[1
]}

Li, Chaofu ^{[1
]}

Gu, Ning ^{[1
]}

Shen, Youcheng ^{[1
]}

Qiu, Zhimei ^{[1
]}

Li, Chaozhong ^{[1
]}

Zhao, Yongchao ^{[1
]}

Zhao, Ranzun ^{[1
]}

机构：

[1] Zunyi Med Univ, Affiliated Hosp, Dept Cardiol, 149 Dalian Rd, Zunyi 563000, Peoples R China

[2] Peoples Hosp Honghuagang Dist, Dept Cardiol, Zunyi, Peoples R China

来源：

CELL TRANSPLANTATION | 2024年 / 33卷

基金：

中国国家自然科学基金;

关键词：

YT521-B homology-domain-containing protein 1; bone marrow mesenchymal stem cells; myocardial infarction; apoptosis; hypoxia and serum deprivation; nuclear factor-kappa-B inhibitor-alpha; C-MYC; PATHWAY; BETA;

D O I：

10.1177/09636897241290910

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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-kappa B) 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.

引用

页数：16

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