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Abstract <p><b>Objective:</b> To investigate the regulatory role and underlying molecular mechanisms of exosomal miR-25-3p in the pathogenesis of sepsis-induced myocardial injury. <b>Methods:</b> Serum exosomes from patients with sepsis-associated myocardial injury (Sepsis-exo) and healthy controls (NC-exo) were isolated and characterized. Using LPS-stimulated AC16 cardiomyocytes as an <i>in vitro</i> model, we evaluated cell viability, apoptosis, mitochondrial function, and organelle dynamics. Bioinformatics tools were employed to predict miR-25-3p target genes, which were subsequently validated using luciferase reporter and RNA immunoprecipitation (RIP) assays. The cardioprotective effects of miR-25-3p were further evaluated <i>in vivo</i> using a cecal ligation and puncture (CLP) mouse model, characterized by echocardiography and histological (HE) staining. <b>Results and Discussion:</b> Sepsis-exo significantly exacerbated LPS-induced cardiomyocyte damage, characterized by decreased cell viability, increased apoptosis, and profound mitochondrial dysfunction. Notably, miR-25-3p was markedly downregulated in Sepsis-exo. Restoration of miR-25-3p levels effectively attenuated these pathological alterations, enhancing cell survival and preserving mitochondrial integrity. Mechanistically, miR-25-3p directly targets and negatively regulates SOX4 expression. Overexpression of SOX4 diminished the protective effects conferred by miR-25-3p. <i>In vivo</i>, administration of a miR-25-3p mimic improved cardiac function and significantly reduced myocardial injury markers. <b>Conclusions:</b> Our findings demonstrate that exosomal miR-25-3p protects against sepsis-induced myocardial injury by targeting SOX4 and maintaining mitochondrial homeostasis. Thus, miR-25-3p represents a promising therapeutic target for the management of sepsis-associated myocardial damage.</p>

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Exosome-Derived miR-25-3p Inhibits Mitochondrial Damage by Targeting SOX4 and Attenuates Sepsis-Induced Myocardial Injury

  • 期刊论文

  • 发表日期：

    2026年6月19日

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  • Rong Huang,
  • Jing Cao,
  • Hongyan Zhao,
  • Weirong Tao,
  • Chao Xu

摘要

Abstract

Objective: To investigate the regulatory role and underlying molecular mechanisms of exosomal miR-25-3p in the pathogenesis of sepsis-induced myocardial injury. Methods: Serum exosomes from patients with sepsis-associated myocardial injury (Sepsis-exo) and healthy controls (NC-exo) were isolated and characterized. Using LPS-stimulated AC16 cardiomyocytes as an in vitro model, we evaluated cell viability, apoptosis, mitochondrial function, and organelle dynamics. Bioinformatics tools were employed to predict miR-25-3p target genes, which were subsequently validated using luciferase reporter and RNA immunoprecipitation (RIP) assays. The cardioprotective effects of miR-25-3p were further evaluated in vivo using a cecal ligation and puncture (CLP) mouse model, characterized by echocardiography and histological (HE) staining. Results and Discussion: Sepsis-exo significantly exacerbated LPS-induced cardiomyocyte damage, characterized by decreased cell viability, increased apoptosis, and profound mitochondrial dysfunction. Notably, miR-25-3p was markedly downregulated in Sepsis-exo. Restoration of miR-25-3p levels effectively attenuated these pathological alterations, enhancing cell survival and preserving mitochondrial integrity. Mechanistically, miR-25-3p directly targets and negatively regulates SOX4 expression. Overexpression of SOX4 diminished the protective effects conferred by miR-25-3p. In vivo, administration of a miR-25-3p mimic improved cardiac function and significantly reduced myocardial injury markers. Conclusions: Our findings demonstrate that exosomal miR-25-3p protects against sepsis-induced myocardial injury by targeting SOX4 and maintaining mitochondrial homeostasis. Thus, miR-25-3p represents a promising therapeutic target for the management of sepsis-associated myocardial damage.