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September 18, 2025Journal of physiological investigation.3 citationsOpen Access

MiR-193b-3p Regulates Gasdermin-D/NLRP3 by Targeting the Signaling Axis Inhibition of Pyroptosis Attenuates Myocardial Ischemia-Reperfusion Injury

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CYChao YuQZQiuping ZhuWXWei Xie

Key Points

  • miR-193b-3p inhibits pyroptosis in myocardial tissue and reduces injury severity, enhancing recovery.
  • The analysis showed a significant decline in cardiac troponin I levels after miR-193b-3p treatment, pointing to its protective role.
  • A myocardial ischemia-reperfusion injury model was used to evaluate pathological changes and confirm the protective effects.
  • The findings indicate that targeting the GSDMD/NLRP3 axis may provide a new strategy for treating ischemia-reperfusion injury.

Abstract

Abstract The complex pathogenesis of myocardial ischemia-reperfusion (I/R) injury is a major factor influencing clinical prognosis. It has been confirmed that microRNAs are involved in myocardial I/R injury, and that pyroptosis is closely associated with its underlying mechanisms. However, the specific mechanism by which miR-193b-3p inhibits cell death and alleviates myocardial I/R injury remains unclear. This study aimed to investigate whether miR-193b-3p can inhibit pyroptosis and protect injured myocardium by targeting the Gasdermin-D (GSDMD)/Nucleotide-binding oligomerization domain-like receptor thermal protein domain-associated protein 3 (NLRP3) signaling axis, thereby offering a potential therapeutic strategy for myocardial I/R injury. Through bioinformatics analysis, pyroptosis-related signaling pathways and key genes involved in myocardial I/R injury were identified. A myocardial I/R injury model was established, and pathological changes in myocardial tissue were evaluated using hematoxylin and eosin staining. A dual-luciferase reporter assay was conducted to verify the targeting relationship between miR-193b-3p and GSDMD. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting were employed to detect mRNA and protein expression levels of miR-193b-3p, GSDMD, and NLRP3. The role of miR-193b-3p in myocardial I/R injury was comprehensively evaluated based on cardiac troponin I levels and the rate of myocardial pyroptosis. The findings confirmed that miR-193b-3p inhibited GSDMD expression, attenuated pathological changes in rat myocardium, downregulated NLRP3 and other pyroptosis-related proteins, and reduced both myocardial pyroptosis and serum cardiac troponin I levels.

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Cite This Study

Yu et al. (2025) studied this question.

synapsesocial.com/papers/68d462b631b076d99fa61948https://doi.org/10.4103/ejpi.ejpi-d-25-00032
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