2. Academic Validation
  3. Exosomes derived from mesenchymal stem cells ameliorate impaired glucose metabolism in myocardial Ischemia/reperfusion injury through miR-132-3p/PTEN/AKT pathway

Exosomes derived from mesenchymal stem cells ameliorate impaired glucose metabolism in myocardial Ischemia/reperfusion injury through miR-132-3p/PTEN/AKT pathway

  • Cell Cycle. 2024 Sep-Oct;23(17-20):893-912. doi: 10.1080/15384101.2025.2485834.
Hongkun Wu 1 2 3,  Yongpeng Hui 2 4,  Xingkai Qian 2 5,  Xueting Wang 6,  Jianwei Xu 7,  Feng Wang 2 4,  Sisi Pan 5,  Kaiyuan Chen 2 4,  Zhou Liu 1 2,  Weilong Gao 1 2,  Jue Bai 4 5,  Guiyou Liang 5
Affiliations

Affiliations

  • 1 School of basic Medicine, Guizhou Medical University, Guiyang, Guizhou, China.
  • 2 Center for Translational Medicine, Guizhou Medical University, Guiyang, Guizhou, China.
  • 3 Department of Cardiac Surgery, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China.
  • 4 School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, China.
  • 5 Department of Cardiac Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
  • 6 The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, University Town, Guiyang, China.
  • 7 National Guizhou Joint Engineering Laboratory for Cell Engineering and Biomedicine Technique, Center for Tissue Engineering and Stem Cell Research, Guizhou Province Key Laboratory of Regenerative Medicine, Guizhou Medical University, Guiyang, China.
PMID: 40181235 DOI: 10.1080/15384101.2025.2485834
Abstract

Exosomes secreted by mesenchymal stem cells (MSCs) have been considered as a novel biological therapy for myocardial ischemia/reperfusion injury (MIRI). However, the underlying mechanism of exosomes has not been completely established, especially in the early stage of MIRI. In this study, we primarily investigated the protective effect of exosomes on MIRI from both in vitro and ex vivo perspectives. Bioinformatic analysis was conducted to identify exosomal miRNA associated with myocardial protection, Genes and proteins related to functional studies and myocardial energy metabolism were analyzed and evaluated using techniques such as Polymerase Chain Re-action (PCR), Western blotting, double luciferase biochemical techniques, flow cytometry assay, etc. It was discovered that exosomes ameliorated cardiomyocyte injury t by delivery of miR-132-3p.This process reduced the expression of Phosphatase and tensin homolog (PTEN) mRNA and protein, enhanced the expression of phosphorylated protein kinase (pAKT), regulated the Insulin signaling pathway, facilitated intracellular Glucose transporter 4 (GLUT4) protein membrane translocation, and enhanced glucose uptake and Adenosine Triphosphate (ATP) production. This study confirmed, for the first time, that MSC-EXO can provide myocardial protection in the early stages of MIRI through miR-132/PTEN/Akt pathway. This research establishes a theoretical and experimental foundation for the clinical application of MSC-derived exosomes.

Keywords

Exosomes; GLUT4; Myocardial ischemia-reperfusion injury; PTEN/AKT; mesenchymal stem cells; miR-132-3p.

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