MiR-21/PTEN Axis Promotes Skin Wound Healing by Dendritic Cells Enhancement

J Cell Biochem. 2017 Oct;118(10):3511-3519. doi: 10.1002/jcb.26026. Epub 2017 May 18.

Abstract

A number of miRNAs associated with wound repair have been identified and characterized, but the mechanism has not been fully clarified. MiR-21 is one of wound-related lncRNAs, and the study aimed to explore the functional involvement of miR-21 and its concrete mechanism in wound healing. In this study, the rat model of skin wounds was established. The expression of miR-21, PTEN and related molecules of wound tissues or cells was determined by quantitative real-time PCR and Western blot, respectively. The regulatory role of miR-21 on PTEN was examined by luciferase reporter gene assay. Flow cytometry assay was applied to measure cell number changes. MiR-21 was upregulated at 6, 24, 48, 72 h after model establishment, and the increase reached a maximum at 24 h in wound tissues. MMP-9 expression presented the same tread as miR-21 and was significantly enhanced within 6 h of wound formation, and then remained to be increased to the maximum at 24 h. The increase of miR-21 was accompanied by the increase of cell total number and DCs ratio in wound fluids. MiR-21 overexpression significantly improved the healing of skin wounds and increased the ratio of DCs in rats. The results of using FL confirmed that miR-21 overexpression obviously promoted DCs differentiation. Additionally, miR-21 could activate AKT/PI3K signaling pathway via inhibition of PTEN. MiR-21 contributes to wound healing via inhibition of PTEN that activated AKT/PI3K signaling pathway to increase DCs. J. Cell. Biochem. 118: 3511-3519, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: AKT/PI3K; DENDRITIC CELLS (DCS); MiR-21; PTEN; WOUND HEALING.

MeSH terms

  • Animals
  • Dendritic Cells / metabolism*
  • Dendritic Cells / pathology
  • Gene Expression Regulation, Developmental
  • Male
  • Matrix Metalloproteinase 9 / biosynthesis
  • MicroRNAs / biosynthesis*
  • PTEN Phosphohydrolase / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction*
  • Skin / metabolism*
  • Skin / pathology
  • Up-Regulation
  • Wound Healing*

Substances

  • MicroRNAs
  • mirn21 microRNA, rat
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • Pten protein, rat
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat