Scholarlink

Objective <p>This study aimed to determine whether dexmedetomidine (DEX) attenuates myocardial ischemia/reperfusion injury (MIRI) by regulating DNA methyltransferase 3B (DNMT3B)–mediated methylation of a CpG island within the Kruppel-like factor 4 (KLF4) promoter.</p> Methods <p>A rat model of MIRI was established and treated with DEX, DNMT3B knockdown, or DEX combined with DNMT3B overexpression. Histopathological alterations, apoptosis, and DNMT3B/KLF4 expression were assessed using H&amp;E staining, TUNEL/cTnT co-staining, RT-qPCR, western blot, immunofluorescence, and immunohistochemistry. H9C2 cardiomyocytes subjected to oxygen-glucose deprivation/reperfusion (OGD/R) were treated with DEX and transfected with DNMT3B or KLF4 knockdown/overexpression plasmids. CpG island methylation within the KLF4 promoter was predicted using MSP and ChIP-PCR.</p> Results <p>MIRI impaired cardiac function, increased infarct size and myocardial enzyme release, upregulated DNMT3B expression, downregulated KLF4 expression, and promoted cardiomyocyte apoptosis. DNMT3B was predominantly localized in cTnT-positive cardiomyocytes. DEX treatment or DNMT3B knockdown reduced DNMT3B expression, restored KLF4 levels, and alleviated myocardial injury <i>in vivo</i> as well as OGD/R-induced damage <i>in vitro</i>. DEX was associated with decreased methylation of the investigated CpG island within the KLF4 promoter. DEX may inhibit DNMT3B-mediated promoter hypermethylation, thereby enhancing KLF4 transcription. KLF4 knockdown abolished the cardioprotective effects of DEX, while DNMT3B overexpression reversed DEX-mediated improvements <i>in vivo</i>.</p> Conclusions <p>DEX may attenuate MI/RI by downregulating DNMT3B and reducing methylation at a CpG island within the KLF4 promoter, thereby promoting KLF4 expression. However, the intrinsic resolution limitations of MSP and ChIP-PCR restrict precise mapping of methylation sites. Higher-resolution techniques, such as whole-genome bisulfite sequencing or single-molecule methylation sequencing, are warranted to validate these findings.</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

Dexmedetomidine Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting DNMT3B-Mediated Hypermethylation of the KLF4 Promoter

  • 期刊论文

  • 发表日期：

    2026年3月10日

查看全文
  • XinJing Chen,
  • Jingxuan Hong

摘要

Objective

This study aimed to determine whether dexmedetomidine (DEX) attenuates myocardial ischemia/reperfusion injury (MIRI) by regulating DNA methyltransferase 3B (DNMT3B)–mediated methylation of a CpG island within the Kruppel-like factor 4 (KLF4) promoter.

Methods

A rat model of MIRI was established and treated with DEX, DNMT3B knockdown, or DEX combined with DNMT3B overexpression. Histopathological alterations, apoptosis, and DNMT3B/KLF4 expression were assessed using H&E staining, TUNEL/cTnT co-staining, RT-qPCR, western blot, immunofluorescence, and immunohistochemistry. H9C2 cardiomyocytes subjected to oxygen-glucose deprivation/reperfusion (OGD/R) were treated with DEX and transfected with DNMT3B or KLF4 knockdown/overexpression plasmids. CpG island methylation within the KLF4 promoter was predicted using MSP and ChIP-PCR.

Results

MIRI impaired cardiac function, increased infarct size and myocardial enzyme release, upregulated DNMT3B expression, downregulated KLF4 expression, and promoted cardiomyocyte apoptosis. DNMT3B was predominantly localized in cTnT-positive cardiomyocytes. DEX treatment or DNMT3B knockdown reduced DNMT3B expression, restored KLF4 levels, and alleviated myocardial injury in vivo as well as OGD/R-induced damage in vitro. DEX was associated with decreased methylation of the investigated CpG island within the KLF4 promoter. DEX may inhibit DNMT3B-mediated promoter hypermethylation, thereby enhancing KLF4 transcription. KLF4 knockdown abolished the cardioprotective effects of DEX, while DNMT3B overexpression reversed DEX-mediated improvements in vivo.

Conclusions

DEX may attenuate MI/RI by downregulating DNMT3B and reducing methylation at a CpG island within the KLF4 promoter, thereby promoting KLF4 expression. However, the intrinsic resolution limitations of MSP and ChIP-PCR restrict precise mapping of methylation sites. Higher-resolution techniques, such as whole-genome bisulfite sequencing or single-molecule methylation sequencing, are warranted to validate these findings.