Adipose mesenchymal stem cell exosomes promote wound healing through accelerated keratinocyte migration and proliferation by activating the AKT/HIF-1α axis

J Mol Histol. 2020 Aug;51(4):375-383. doi: 10.1007/s10735-020-09887-4. Epub 2020 Jun 19.

Abstract

Accelerating wound healing is a key consideration for surgeons. The three stages of wound healing include the inflammatory response, cell proliferation and tissue repair, and much research has focused on the migration and proliferation of epidermal cells, since this is one of the most important steps in wound healing. Studies have shown that adipose mesenchymal stem cells (ADSCs) can promote wound healing by releasing exosomes, although the specific mechanism remains unclear. To clarify the role of adipose mesenchymal stem cell exosomes (ADSCs-exo), we constructed a HaCaT cells model and a mouse wound healing model to examine the effects of ADSCs-exo on wound healing. CCK8 assays and the scratch test showed that ADSCs-exo could promote the proliferation and migration of HaCaT cells. Western blotting and real-time PCR showed that ADSCs-exo upregulated the phosphorylation of AKT and the expression of HIF-1α in HaCaT cells. HIF-1α expression was reduced by inhibiting AKT phosphorylation,and the migration of HaCaT cells simultaneously slowed. These results were also confirmed in vivo. In conclusion, we confirmed that ADSCs-exo promote the proliferation and migration of HaCaT cells by regulating the activation of the AKT/HIF-1α signaling pathway, thus promoting wound healing.

Keywords: AKT; Adipose mesenchymal stem cell; Exosome; HIF-1α; Wound healing.

MeSH terms

  • Adipose Tissue / metabolism
  • Adipose Tissue / physiology*
  • Adult
  • Animals
  • Cell Line
  • Cell Movement / physiology*
  • Cell Proliferation / physiology*
  • Exosomes / metabolism
  • Exosomes / physiology*
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / physiology
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Keratinocytes / metabolism
  • Keratinocytes / physiology
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Models, Animal
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / physiology
  • Skin / metabolism
  • Skin / physiopathology
  • Up-Regulation / physiology
  • Wound Healing / physiology*
  • Young Adult

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Proto-Oncogene Proteins c-akt