{"title":"Exosomal miR-98-5p Derived from Bone Marrow Mesenchymal Stem Cells Alleviates Myocardial Infarction by Regulating Autophagy via Targeting E2F6.","authors":"Haifei Xu, Wei Zhang","doi":"","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To investigate the effect of exosomal miR-98-5p derived from bone marrow mesenchymal stem cells (BMSCs) on cardiomyocyte injury in acute myocardial infarction (AMI) and analyze its mechanism of action.</p><p><strong>Methods: </strong>An AMI model in rats was established via ligation of the left anterior descending (LAD) coronary artery. Cardiac systolic function was assessed via echocardiography. Histopathological alterations in myocardial tissue were evaluated by hematoxylin and eosin (HE) staining, while the extent of myocardial infarction was determined through triphenyltetrazolium chloride (TTC) staining. Serum levels of CK-MB, cTnT, and LDH were quantified through ELISA. An AMI cell model was established by subjecting H9C2 cardiomyoblasts to hypoxic conditions. Exosomes were isolated from BMSCs, and their effects on cardiomyocyte injury were investigated. Cellular autophagy levels were examined via western blot (WB). The regulatory interplay between miR-98-5p and E2F6 was validated via a dual-luciferase reporter (DLR) assay.</p><p><strong>Results: </strong>In comparison to the Sham group, myocardial tissue in rats with AMI exhibited significant structural damage, accompanied by reduced autophagic activity and reduced expression of miR-98-5p. In comparison to the AMI + phosphate-buffered saline (PBS) group, treatment with BMSCs-derived exosomes (BMSCs-exo) markedly improved cardiac function and further enhanced autophagy in AMI rats. <i>In vitro</i>, cells subjected to hypoxic conditions displayed diminished viability and proliferative capacity, increased apoptosis, impaired autophagy, and decreased miR-98-5p expression relative to the control group. However, administration of BMSCs-exo restored miR-98-5p expression, mitigated cellular injury, and promoted autophagic activity. Notably, these protective influences were reversed by the addition of the autophagy inhibitor 3-methyladenine (3-MA). DLR assays confirmed a direct regulatory interaction between miR-98-5p and E2F6. Suppression of miR-98-5p resulted in the upregulation of E2F6, thereby attenuating the reparative effects of BMSCs-exo on myocardial tissue and inhibiting autophagy.</p><p><strong>Conclusion: </strong>BMSCs-exo miR-98-5p ameliorates AMI-induced myocardial injury by regulating cardiomyocyte autophagy through targeting E2F6.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":"55 4","pages":"481-495"},"PeriodicalIF":1.0000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of clinical and laboratory science","FirstCategoryId":"3","ListUrlMain":"","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: To investigate the effect of exosomal miR-98-5p derived from bone marrow mesenchymal stem cells (BMSCs) on cardiomyocyte injury in acute myocardial infarction (AMI) and analyze its mechanism of action.
Methods: An AMI model in rats was established via ligation of the left anterior descending (LAD) coronary artery. Cardiac systolic function was assessed via echocardiography. Histopathological alterations in myocardial tissue were evaluated by hematoxylin and eosin (HE) staining, while the extent of myocardial infarction was determined through triphenyltetrazolium chloride (TTC) staining. Serum levels of CK-MB, cTnT, and LDH were quantified through ELISA. An AMI cell model was established by subjecting H9C2 cardiomyoblasts to hypoxic conditions. Exosomes were isolated from BMSCs, and their effects on cardiomyocyte injury were investigated. Cellular autophagy levels were examined via western blot (WB). The regulatory interplay between miR-98-5p and E2F6 was validated via a dual-luciferase reporter (DLR) assay.
Results: In comparison to the Sham group, myocardial tissue in rats with AMI exhibited significant structural damage, accompanied by reduced autophagic activity and reduced expression of miR-98-5p. In comparison to the AMI + phosphate-buffered saline (PBS) group, treatment with BMSCs-derived exosomes (BMSCs-exo) markedly improved cardiac function and further enhanced autophagy in AMI rats. In vitro, cells subjected to hypoxic conditions displayed diminished viability and proliferative capacity, increased apoptosis, impaired autophagy, and decreased miR-98-5p expression relative to the control group. However, administration of BMSCs-exo restored miR-98-5p expression, mitigated cellular injury, and promoted autophagic activity. Notably, these protective influences were reversed by the addition of the autophagy inhibitor 3-methyladenine (3-MA). DLR assays confirmed a direct regulatory interaction between miR-98-5p and E2F6. Suppression of miR-98-5p resulted in the upregulation of E2F6, thereby attenuating the reparative effects of BMSCs-exo on myocardial tissue and inhibiting autophagy.
Conclusion: BMSCs-exo miR-98-5p ameliorates AMI-induced myocardial injury by regulating cardiomyocyte autophagy through targeting E2F6.
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