ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Tissue Engineering and Regenerative Medicine
Exosomes derived from miR-26a-5p-modified adipose mesenchymal stem cells improve wound healing by targeting MAP2K4
Provisionally accepted
- 1Department of Plastic and Cosmetic Surgery, Ningbo NO.2 Hospital, Ningbo, China
- 2Department of Hepatobiliary Pancreatic Surgery, Ningbo NO.2 Hospital, Ningbo, China
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Introduction: Abnormal wound healing impairs bodily functions and burdens healthcare systems. Adipose mesenchymal stem cells (AMSCs)-derived exosomes promote wound healing, with exosomal microRNAs (miRNAs) playing pivotal roles. This study investigated the roles and mechanisms of miR-26a-5p (delivered by AMSCs-derived exosomes) in wound healing. Methods: The GSE55661 dataset was analyzed to screen a crucial miRNA (miR-26a-5p) and its target gene (MAP2K4), and their interaction was further validated by dual-luciferase reporter gene assay. Exosomes were isolated from miR-26a-5p-overexpressing AMSCs, and a mouse skin defect model was used to evaluate their effects on wound healing. Results: Bioinformatics identified 13 differentially expressed miRNAs, and a miRNA-mRNA regulatory network composed of 12 DEmiRNAs and 143 regulated target genes was built. In this network, miR-26a served as the hub node, and the target genes were enriched in the MAPK cascade, as well as cAMP, relaxin, Hippo, Apelin, Wnt, and cGMP-PKG signaling pathways. Thereafter, MAP2K4 was identified as the target of miR-26a-5p, and exosomes were successfully isolated from AMSCs overexpressing miR-26a-5p. Exosomes from miR-26a-5p overexpressed AMSCs (like miR-26a-5p agomir) could facilitate wound healing, and down-regulated MAP2K4, Il6, Il1β, and Tnf-α, whereas up-regulated Col1a1, Cd31, Col2a1, α-Sma, and Col3a1. Discussion: AMSCs-derived exosomes delivering miR-26a-5p may expedite wound healing by targeting MAP2K4, inhibiting inflammation, and enhancing angiogenesis and ECM synthesis.
Keywords: AMSCs-derived exosomes, miR-26a-5p, MAP2K4, Angiogenesis, Wound Healing
Received: 08 Jul 2025; Accepted: 27 Oct 2025.
Copyright: © 2025 Chen, Ye, Chi and Xie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shujie Xie, siabc83@163.com
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