MicroRNA-21 increases the expression level of occludin through regulating ROCK1 in prevention of intestinal barrier dysfunction

J Cell Biochem. 2019 Mar;120(3):4545-4554. doi: 10.1002/jcb.27742. Epub 2018 Oct 9.

Abstract

Objective: The aim of this study is to investigate the role of molecular mechanism of microRNA (miR)-21 on tight junction (TJ)-proteins and its protective effects on the intestinal barrier.

Methods: TJ proteins and target genes expression were analyzed in miR-21 inhibition and overexpression NCM460 cell lines. To further verify the role of miR-21, the mmu-miR-21 intestinal epithelial conditional knockout (IKO) mice model was established. MiR-21 expression was detected in clinical specimens of acute stercoral obstruction patients.

Results: Rho-associated protein kinase 1 (ROCK1) were identified as target genes of miR-21. There is a negative correlation between miR-21 expression level and TJ proteins levels. TJ protein and ROCK1 were significantly decreased in miR-21 IKO mice, which presented intestinal inflammation response and intestinal barrier dysfunction (both P < 0.05). Determination of clinical samples showed consistent results with NCM460 cell line and miR-21 IKO mice.

Conclusions: MiR-21 could be a protective factor of intestinal barrier dysfunction, which promoting the expression of TJ protein by targeting ROCK1 in vivo and in vitro.

Keywords: ROCK1; intestinal barrier; intestinal conditional knockout mice; microRNA-21; occludin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Intestinal Mucosa / metabolism*
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Occludin / biosynthesis*
  • Occludin / genetics
  • Tight Junctions / genetics
  • Tight Junctions / metabolism
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism*

Substances

  • MIRN21 microRNA, human
  • MIRN21 microRNA, mouse
  • MicroRNAs
  • OCLN protein, human
  • Occludin
  • Ocln protein, mouse
  • ROCK1 protein, human
  • Rock1 protein, mouse
  • rho-Associated Kinases