miR-92a-1-5p targets MEF2A to induce insulin resistance in myocardial ischemia/reperfusion injury
- Biochem Biophys Res Commun. 2025 Jul 1:768:151938. doi: 10.1016/j.bbrc.2025.151938.
- 1. Division of Cardiac Surgery, Guizhou Institute of Precision Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550009, China; Translational Medicine Research Center, Guizhou Province Key Laboratory of Regenerative Medicine, Tissue Engineering and Stem Cell Experiment Center, Guizhou Medical University, GuiAn, 561113, Guizhou, China.
- 2. Department of Anesthesiology, The Affiliated JinYang Hospital of Guizhou Medical University, The Second People's Hospital of Guiyang, Guiyang, 550023, Guizhou, China.
- 3. Division of Cardiac Surgery, Guizhou Institute of Precision Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550009, China.
- 4. Translational Medicine Research Center, Guizhou Province Key Laboratory of Regenerative Medicine, Tissue Engineering and Stem Cell Experiment Center, Guizhou Medical University, GuiAn, 561113, Guizhou, China.
- 5. Division of Cardiac Surgery, Guizhou Institute of Precision Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550009, China. Electronic address: [email protected].
- 6. Division of Cardiac Surgery, Guizhou Institute of Precision Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550009, China; Translational Medicine Research Center, Guizhou Province Key Laboratory of Regenerative Medicine, Tissue Engineering and Stem Cell Experiment Center, Guizhou Medical University, GuiAn, 561113, Guizhou, China; Department of Pharmacology, School of Basic Medical Sciences, Guizhou Medical University, GuiAn, 561113, Guizhou, China. Electronic address: [email protected].
Purpose: Improving myocardial energy metabolism is an important way to alleviate myocardial ischemia/reperfusion injury (MIRI). Myocardial Insulin resistance (IR) can occur after MIRI and cause the inhibition of glucose absorption and metabolism. This study aimed to detect the mechanism of miR-92a-1-5p in MIRI-induced myocardial IR.
Methods: First, MIRI rat models were established using the Langendorff technique. H9c2 cells were treated with oxygen-glucose deprivation/reperfusion (OGD/R) to establish in vitro cell models. The expression levels of miR-92a-1-5p and myocyte enhancer factor 2A (MEF2A) were detected using RT-qPCR, and the expression of glucose transporter 4 (GLUT4) in the cell membrane and MEF2A was detected using Western blot. Immunofluorescence was used to detect GLUT4 expression in the cell membrane of H9c2 cells. Glucose absorption was detected in H9c2 cells using flow cytometry. H&E staining was used to determine pathological changes in heart tissue. H9c2 cell viability was detected using CCK-8 assay, and the binding affinity between miR-92a-1-5p and MEF2A was verified using dual luciferase reporter assay.
Results: miR-92a-1-5p expression increased, and MEF2A expression decreased after OGD/R in H9c2 cells or MIRI in rats. Overexpression of miR-92a-1-5p aggravated myocardial tissue and H9c2 cell damage, inhibited the translocation of GLUT4 to the cell membrane, and reduced glucose absorption. Inhibiting the miR-92a-1-5p yielded the opposite results. MEF2A overexpression reversed the injury, which was exacerbated by miR-92a-1-5p, and promoted the translocation of GLUT4 to the cell membrane and glucose absorption. The double luciferase reporter assay results showed that miR-92a-1-5p could negatively regulate the expression of MEF2A.
Conclusion: miR-92a-1-5p expression increased after IR in myocardial tissue and H9c2 cells. Inhibition of miR-92a-1-5p increased MEF2A expression, promoted GLUT4 translocation, and increased glucose absorption, thereby reducing MIRI.
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Cat. No.Product NameDescriptionTargetResearch Area
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target: Fluorescent DyeResearch Areas: Others