miR-93‑mediated collagen expression in stress urinary incontinence via calpain-2

Mol Med Rep. 2018 Jan;17(1):624-629. doi: 10.3892/mmr.2017.7910. Epub 2017 Oct 26.

Abstract

The aim of the present study was to investigate the expression and mechanism of microRNA (miR)‑93 in collagen expression in stress urinary incontinence (SUI). Vaginal tissue, primary fibroblasts and SUI primary fibroblasts were obtained to detect the expression of miR‑93, interstitial collagenase (MMP1), collagen I and calpain‑2. Reverse transcription‑quantitative polymerase chain reaction analysis was performed to detect the levels of miR‑93 and MMP1. Western blotting was used to evaluate the protein levels of calpain‑2, MMP1 and collagen I. MMP1 and hydroxyproline levels in the supernatant were measured by ELISA. The association between miR‑93 and calpain‑2 was investigated by luciferase reporter assays. The expression of miR‑93 and collagen I was significantly downregulated in the SUI group, while the expression of calpain‑2 and MMP1 was significantly upregulated. ELISA analysis demonstrated that the MMP1 level increased and the hydroxyproline level decreased in the SUI group. Additionally, calpain‑2 was identified to be a target of miR‑93, and miR‑93 was able to negatively regulate the expression of calpain‑2. Restoration of calpain‑2 in miR‑93‑overexpresseing SUI primary fibroblasts reversed the alteration in hydroxyproline expression, indicating that calpain‑2 was negatively associated with collagen expression. The results of the present study suggested that miR‑93 regulated MMP1 and collagen I expression in fibroblasts via calpain‑2. miR‑93 mediated collagen expression in stress urinary incontinence via calpain‑2.

MeSH terms

  • Calpain / genetics*
  • Collagen Type I / genetics*
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Gene Expression Regulation / genetics
  • Humans
  • Matrix Metalloproteinase 1 / genetics
  • MicroRNAs / genetics*
  • Middle Aged
  • Urinary Incontinence, Stress / genetics*
  • Urinary Incontinence, Stress / pathology
  • Vagina / metabolism
  • Vagina / pathology

Substances

  • Collagen Type I
  • MIRN93 microRNA, human
  • MicroRNAs
  • Calpain
  • CAPN2 protein, human
  • MMP1 protein, human
  • Matrix Metalloproteinase 1