Upregulation of miRNA-1228-3p alleviates TGF-β-induced fibrosis in renal tubular epithelial cells

Histol Histopathol. 2020 Oct;35(10):1125-1133. doi: 10.14670/HH-18-242. Epub 2020 Jul 28.

Abstract

Background: Chronic kidney disease (CKD) has become a major public health issue, which can lead to renal fibrosis regardless of the initial injury. It has been previously reported that miRNA-1228-3p was correlate with the progression of kidney fibrosis. However, the mechanism by which miRNA-1228-3p regulates renal fibrosis remains unclear.

Methods: Renal tubular epithelial cells (HK-2) were treated with TGF-β1 (10 ng/ml) in an in vitro model of renal fibrosis. Gene and protein expressions in HK-2 cells were measured by Western-blot and RT-qPCR, respectively. The relation between miRNA-1228-3p and its target gene was investigated by dual luciferase report analysis.

Results: Upregulation of miRNA-1228-3p significantly inhibited TGF-β1-induced fibrosis of HK-2 cells in vitro by targeting GDF11. In addition, miRNA-1228-3p exhibited anti-fibrosis effect through inhibition of the smad2/smad4 signaling pathway.

Conclusion: Upregulation of miRNA-1228-3p markedly inhibited the progression of renal fibrosis in vitro, indicating that miRNA-1228-3p may serve as a potential novel target for the treatment of renal fibrosis.

MeSH terms

  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism
  • Cell Line
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Fibrosis
  • Growth Differentiation Factors / genetics
  • Growth Differentiation Factors / metabolism
  • Humans
  • Kidney Tubules, Proximal / drug effects*
  • Kidney Tubules, Proximal / metabolism
  • Kidney Tubules, Proximal / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Signal Transduction
  • Smad2 Protein / genetics
  • Smad2 Protein / metabolism
  • Smad4 Protein / genetics
  • Smad4 Protein / metabolism
  • Transforming Growth Factor beta1 / toxicity*
  • Up-Regulation

Substances

  • Bone Morphogenetic Proteins
  • GDF11 protein, human
  • Growth Differentiation Factors
  • MIRN1228 microRNA, human
  • MicroRNAs
  • SMAD2 protein, human
  • SMAD4 protein, human
  • Smad2 Protein
  • Smad4 Protein
  • Transforming Growth Factor beta1