Inhibition of exosomal miR-24-3p in diabetes restores angiogenesis and facilitates wound repair via targeting PIK3R3

J Cell Mol Med. 2020 Dec;24(23):13789-13803. doi: 10.1111/jcmm.15958. Epub 2020 Nov 3.

Abstract

Diabetic foot ulcer (DFU) is one of the common ailments of elderly people suffering from diabetes. Exosomes containing various active regulators have been found to play a significant role in apoptosis, cell proliferation and other biological processes. However, the effect and the underlying mechanism of action of diabetes patients derived from circulating exosomes (Dia-Exos) on DFU remain unclear. Herein, we aim to explore the potential regulatory role of Dia-Exos. First, we attempted to demonstrate the harmful effect of Dia-Exos both in vivo and in vitro. miRNA-24-3p (miR-24-3p) was found enriched with Dia-Exos. Hence, inhibition of this miRNA could partially reverse the negative effect of Dia-Exos, thus, in ture, accelerates wound repair. Luciferase assay further verified the binding of miR-24-3p to the 3'-UTR of phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3) mRNA and the PIK3R3 expression enhanced human umbilical vein endothelial cells functionality in vitro. Hence, the findings of this study reveal the regulatory role of Dia-Exos in the process of wound healing and provide experimental evidence for the therapeutic effects of knocking down miR-24-3p in DFU treatment.

Keywords: PIK3R3; human umbilical vein endothelial cells; miRNA; wound repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus
  • Exosomes / metabolism*
  • Exosomes / ultrastructure
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Male
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neovascularization, Physiologic / genetics*
  • Phosphatidylinositol 3-Kinases / genetics*
  • Phosphatidylinositol 3-Kinases / metabolism
  • RNA Interference*
  • Wound Healing / genetics*

Substances

  • MIRN24 microRNA, human
  • MicroRNAs
  • PIK3R3 protein, human