MicroRNA-101 protects bladder of BOO from hypoxia-induced fibrosis by attenuating TGF-β-smad2/3 signaling

IUBMB Life. 2019 Feb;71(2):235-243. doi: 10.1002/iub.1968. Epub 2018 Dec 13.

Abstract

Bladder outlet obstruction is a common disease, which always evokes urinary bladder wall remodeling significantly. It has been suggested that bladder outlet obstruction can make the bladder progression from inflammation to fibrosis, and hypoxia may play a vital role. It has been found the expression of microRNA-101 varied in bladder after BOO. But what role microRNA-101 and hypoxia play in bladder is not well known. This study is to investigate the mechanism of microRNA-101 and hypoxia in fibrosis of bladder after BOO. We found the expression of microRNA-101 and hif-1α increased in bladder after BOO. Hypoxia could promote the expression of extracellular matrix subtypes and microRNA-101 in BSMCs. When microRNA-101b was translated into BSMCs, the smad2/3 signaling pathway was found to repress. Dual luciferase reporter detected that microRNA-101b attenuated the TGF-β signaling pathway by inhibiting the expression of TGFβR1. Then, we conclude microRNA-101b is induced by hypoxia and represses fibrosis of BSMCs by inhibiting the expression of TGFβR1 through TGF-β signaling pathway, and it may be an anti-fibrotic miRNA for therapy. © 2018 IUBMB Life, 71(1):235-243, 2019.

Keywords: MiR-101; Tgfβr1; bladder fibrosis; bladder outlet obstruction; bladder smooth muscle cells; hypoxia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology
  • Fibrosis
  • Gene Expression Regulation
  • Genes, Reporter
  • Humans
  • Hypoxia / complications
  • Hypoxia / genetics*
  • Hypoxia / metabolism
  • Hypoxia / pathology
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Luciferases / genetics
  • Luciferases / metabolism
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology
  • Primary Cell Culture
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Transforming Growth Factor-beta Type I / genetics
  • Receptor, Transforming Growth Factor-beta Type I / metabolism
  • Signal Transduction
  • Smad2 Protein / genetics*
  • Smad2 Protein / metabolism
  • Smad3 Protein / genetics*
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta1 / genetics*
  • Transforming Growth Factor beta1 / metabolism
  • Urinary Bladder / metabolism
  • Urinary Bladder / pathology
  • Urinary Bladder Neck Obstruction / complications
  • Urinary Bladder Neck Obstruction / genetics*
  • Urinary Bladder Neck Obstruction / metabolism
  • Urinary Bladder Neck Obstruction / pathology

Substances

  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MIRN101 microRNA, rat
  • MicroRNAs
  • Smad2 Protein
  • Smad2 protein, rat
  • Smad3 Protein
  • Smad3 protein, rat
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta1
  • Luciferases
  • Receptor, Transforming Growth Factor-beta Type I
  • Tgfbr1 protein, rat