Function of intestinal barrier protected by regulating the miR-199a-3p in ulcerative colitis: Modulation of IL-23/IL-17A axis

Fundam Clin Pharmacol. 2021 Oct;35(5):852-860. doi: 10.1111/fcp.12650. Epub 2021 Mar 4.

Abstract

Ulcerative colitis is a chronic inflammatory bowel disorder, which is having higher mortality rate. The present report evaluates the protective effect of miR-199a-3p oligomer for the treatment of Ulcerative colitis (UC). Ulcerative colitis was induced by administration of dextran sulfate sodium [DSS (3%)] with drinking water for the duration of one week in mice and miR-199a-3p oligomer was treated for the same duration. Effect of miR-199a-3p oligomer was determined by estimating the body weight, blood stool and length of colon in UC mice. Inflammatory cytokines, oxidative stress parameters and Treg/Th17 ratio was determined in the serum, intestinal and spleen tissue of UC mice. mRNA expression of TGFβ, Foxp3, RORγt and STAT3 was estimated in the intestinal tissue of UC mice. Moreover, permeability of intestine was determined by estimating the expression of FITC-dextran in the serum and expression of junction protein in the tissue of UC mice. The data of the study suggest that treatment with miR-199a-3p oligomer ameliorates the altered condition in ulcerative colitis mice. There was reduction in the level of cytokines and parameters of oxidative stress in the intestine of miR-199a-3p oligomer than UC group. Moreover, intestinal permeability was enhanced in miR-199a-3p oligomer treated UC mice. The level of Th17 in the serum and mRNA expression of TGFβ, Foxp3, RORγt and STAT3 was attenuated in miR-199a-3p oligomer treated UC mice. In conclusion, the data of the study suggest that treatment with miR-199a-3p oligomer ameliorates intestinal barrier in ulcerative colitis by down regulating the IL-17A/IL-23 axis.

Keywords: inflammation; interleukin; miR-199a-3p; oxidative stress; ulcerative colitis.

MeSH terms

  • Animals
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / therapy*
  • Dextran Sulfate
  • Disease Models, Animal
  • Interleukin-17 / metabolism
  • Interleukin-23 / metabolism
  • Intestines / drug effects
  • Intestines / metabolism
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / therapeutic use*
  • Signal Transduction / drug effects

Substances

  • Interleukin-17
  • Interleukin-23
  • MicroRNAs
  • Mirn199 microRNA, mouse
  • Dextran Sulfate