MicroRNA-29b inhibits TGF-β1-induced fibrosis via regulation of the TGF-β1/Smad pathway in primary human endometrial stromal cells

Mol Med Rep. 2016 May;13(5):4229-37. doi: 10.3892/mmr.2016.5062. Epub 2016 Mar 30.

Abstract

Transforming growth factor (TGF)‑β1 has a key role in the regulation of fibrosis and organ dysfunction. During the pathogenesis and progression of vital organ fibrosis, the microRNA (miR)‑29 family is irregularly downregulated and exogenous supplementation of miR‑29b has a strong anti‑fibrotic capacity. However, whether TGF‑β1 is able to provoke endometrial fibrosis, and the role of miR‑29 in endometrial fibrosis remain unclear. In the present study, RT‑qPCR, immunocytochemistry, western blot analysis, scanning electron microscopy, immunofluorescence staining, cell proliferation assay and flow cytometric analysis were employed. The results demonstrated that the expression levels of collagen, type 1, alpha 1 (COL1A1), α‑smooth muscle actin (α‑SMA) and phosphorylated (p)‑Smad2/3 were increased, whereas miR‑29b and maternally expressed gene 3 (MEG3) were decreased in primary endometrial stromal cells (ESCs) in response to TGF‑β1 stimulation, in a time and dose‑dependent manner. Furthermore, overexpression of miR‑29b markedly reduced the expression levels of COL1A1 and α‑SMA, and decreased the expression and nuclear accumulation of p‑Smad2/3. In addition, ectopic overexpression of miR‑29b increased the expression levels of MEG3, inhibited myofibroblast‑like cell proliferation and induced apoptosis. These findings indicated that miR‑29b may have a significant anti‑fibrotic role, and may attenuate TGF‑β1‑induced fibrosis in ESCs. Therefore, exogenous miR‑29b may serve as a potential therapeutic agent for the treatment of endometrial fibrosis.

MeSH terms

  • Adult
  • Cells, Cultured
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Endometrium / metabolism*
  • Endometrium / pathology
  • Female
  • Fibrosis
  • Gene Expression Regulation
  • Humans
  • MicroRNAs / metabolism*
  • Middle Aged
  • Signal Transduction*
  • Smad2 Protein / metabolism*
  • Smad3 Protein / biosynthesis
  • Smad3 Protein / metabolism*
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • MIRN29a microRNA, human
  • MicroRNAs
  • SMAD2 protein, human
  • SMAD3 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • TGFB1 protein, human
  • Transforming Growth Factor beta1