The bone mesenchymal stem cell-derived exosomal miR-146a-5p promotes diabetic wound healing in mice via macrophage M1/M2 polarization.

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  • Additional Information
    • Source:
      Publisher: North Holland Publishing Country of Publication: Ireland NLM ID: 7500844 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-8057 (Electronic) Linking ISSN: 03037207 NLM ISO Abbreviation: Mol Cell Endocrinol Subsets: MEDLINE
    • Publication Information:
      Publication: Limerick : North Holland Publishing
      Original Publication: Amsterdam, North-Holland.
    • Subject Terms:
      Mesenchymal Stem Cells*/metabolism ; MicroRNAs*/genetics ; Diabetes Complications*/genetics ; Diabetes Complications*/metabolism ; Wound Healing*/genetics; Animals ; Humans ; Mice ; Diabetes Mellitus/pathology ; Human Umbilical Vein Endothelial Cells ; Macrophages ; TNF Receptor-Associated Factor 6 ; Exosomes/genetics
    • Abstract:
      A diabetic wound is a refractory disease that afflicts patients globally. MicroRNA-146a-5p (miR-146a-5p) is reported to represent a potential therapeutic target for diabetic wounds. However, microRNA easily degrades in the wound microenvironment. This study extracted bone marrow mesenchymal stem cell (BMSC)-derived exosomes (EXO). Electroporation technology was used to load miR-146a-5p into EXO (labeled as EXO-miR-146a). The endothelial cells (human umbilical vein endothelial cells [HUVECs]) and macrophages were cocultured in transwell chambers in the presence of high glucose. Cell proliferation, migration, and angiogenesis were measured with cell counting kit 8, scratch, and tube forming assays, respectively. Flow cytometry was introduced to validate the biomarker of macrophages and BMSCs. The expression level of macrophage polarization-related proteins and tumor necrosis factor receptor-associated factor 6 (TRAF6) was assessed with western blotting analysis. The full-thickness skin wound model was developed to verify the in vitro results. EXO-miR-146a promoted the proliferation, migration, and angiogenesis of HUVECs in the hyperglycemic state by suppressing the TRAF6 expression in vitro. Additionally, EXO-miR-146a treatment facilitated M2 but inhibited M1 macrophage polarization. Furthermore, EXO-miR-146a enhances reepithelialization, angiogenesis, and M2 macrophage polarization, thereby accelerating diabetic wound healing in vivo. The EXO-miR-146a facilitated M2 macrophage polarization, proliferation, migration, and angiogenesis of HUVECs through TRAF6, thereby ameliorating intractable diabetic wound healing. These results established the basis for using EXO to deliver drugs and revealed mediators for diabetic wound treatment.
      Competing Interests: Declaration of competing interest The authors report no conflict of interest.
      (Copyright © 2023 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Angiogenesis; BMSCs; Diabetic wound healing; EXO-miR-146a; TRAF6
    • Accession Number:
      0 (MicroRNAs)
      0 (TNF Receptor-Associated Factor 6)
      0 (Mirn146 microRNA, mouse)
    • Publication Date:
      Date Created: 20231020 Date Completed: 20231216 Latest Revision: 20240412
    • Publication Date:
      20240412
    • Accession Number:
      10.1016/j.mce.2023.112089
    • Accession Number:
      37863468