Scholarlink

<p>Diabetic cardiomyopathy (DCM) is an irreversible chronic cardiovascular complication of diabetes with a high mortality rate. This study aimed to explore the role of methyltransferase-like 14 (METTL14)-mediated m6A modification in DCM. Here, DCM mouse models and high glucose (HG)-induced H9C2 cell models were employed. Cell phenotype was assessed using CCK-8 assay, lactate dehydrogenase (LDH) assay, Western blot, and flow cytometry. The underlying mechanism was investigated using quantitative real-time PCR (qPCR), methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and dual-luciferase reporter assay. The results showed that METTL14 was upregulated in vitro and in vivo. Downregulation of METTL14 inhibited pyroptosis and myocardial damage. Mechanistically, METTL14 enhanced NLRP3 stability through m6A modification of NLRP3. Moreover, the m6A reader protein YTHDF1 (YTH N6-methyladenosine RNA-binding protein 1) mediated NLRP3 upregulation. This study revealed a novel mechanism by which METTL14-mediated m6A methylation regulates DCM progression, providing a potential therapeutic target for DCM.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

METTL14 aggravates pyroptosis in diabetic cardiomyopathy by promoting m6A modification of NLRP3

  • 期刊论文

  • 发表日期：

    2025年10月15日

查看全文
  • Zhao Hua,
  • Fangjie Zhong,
  • Chaofen Xu,
  • Shuyi Liang

摘要

Diabetic cardiomyopathy (DCM) is an irreversible chronic cardiovascular complication of diabetes with a high mortality rate. This study aimed to explore the role of methyltransferase-like 14 (METTL14)-mediated m6A modification in DCM. Here, DCM mouse models and high glucose (HG)-induced H9C2 cell models were employed. Cell phenotype was assessed using CCK-8 assay, lactate dehydrogenase (LDH) assay, Western blot, and flow cytometry. The underlying mechanism was investigated using quantitative real-time PCR (qPCR), methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and dual-luciferase reporter assay. The results showed that METTL14 was upregulated in vitro and in vivo. Downregulation of METTL14 inhibited pyroptosis and myocardial damage. Mechanistically, METTL14 enhanced NLRP3 stability through m6A modification of NLRP3. Moreover, the m6A reader protein YTHDF1 (YTH N6-methyladenosine RNA-binding protein 1) mediated NLRP3 upregulation. This study revealed a novel mechanism by which METTL14-mediated m6A methylation regulates DCM progression, providing a potential therapeutic target for DCM.