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Huanhuan Sun, Jueqiong Wang, Wei Bi, Feng Zhang, Kai Zhang, Xitao Tian, Xiang Gao, Yanrong Zhang, Mesenchymal stem cell-derived exosomal microRNA-367-3p mitigates lower limb ischemia/reperfusion injury in mouse skeletal muscle via EZH2 targeting, Journal of Pharmacy and Pharmacology, Volume 76, Issue 12, December 2024, Pages 1634–1646, https://doi.org/10.1093/jpp/rgae086
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Abstract
This study aimed to investigate the protective effect of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-exo) against lower limb ischemia/reperfusion (I/R) injury-induced pyroptosis in skeletal muscle.
A mouse model of lower limb I/R injury was utilized to assess the impact of BMSCs-exo, particularly when loaded with microRNA-367-3p (miR-367-3p), on pyroptosis. Histological examination, wet weight/dry weight ratio measurements, and luciferase assays were employed to elucidate the mechanisms involved.
BMSCs-exo effectively suppressed pyroptosis in injured skeletal muscle tissue. Loading BMSCs-exo with miR-367-3p enhanced this protective effect by downregulating key pyroptosis-related proteins. Luciferase assays identified enhancer of zeste homolog 2 (EZH2) as a direct target of miR-367-3p in BMSCs-exo.
BMSCs-exo loaded with miR-367-3p safeguarded mouse skeletal muscle against pyroptosis-induced I/R injury by targeting EZH2. These findings offer valuable insights into potential therapeutic strategies for lower limb I/R injuries, emphasizing the therapeutic potential of BMSCs-exo in mitigating tissue damage caused by pyroptosis.