MiR-21 relieves rheumatoid arthritis in rats via targeting Wnt signaling pathway

Eur Rev Med Pharmacol Sci. 2019 Aug;23(3 Suppl):96-103. doi: 10.26355/eurrev_201908_18635.

Abstract

Objective: To investigate the influence of micro ribonucleic acid (miR)-21 on rats with rheumatoid arthritis (RA) through the Wnt signaling pathway.

Materials and methods: A total of 30 rats were divided into three groups: control group (healthy rats, n=10), model group (rat model of RA, n=10), and MiR group (rat model of RA injected with miR-21 lentivirus, n=10). The paw volume, arthritis indexes, and protein expression level in each group were analyzed by means of paw volume and arthritis index measurement, reverse transcription-polymerase chain reaction (RT-PCR) assay, and fluorescent Western blotting.

Results: The expression levels of inflammatory factors declined in MiR group compared with those in model group, while they were higher in model group than those in control group and MiR group (p<0.05). At 15 d after transfection with lentivirus, the paw volume in MiR group was smaller than that in model group, which was decreased markedly with the extended time of transfection (p<0.05). On the 30th d, MiR group had a remarkably smaller paw volume than model group. In comparison with that in control group, the paw volume in model group was increased notably from the 7th d and displayed a significant difference in the 30th d (p<0.05). The arthritis indexes in MiR group were lower than those in model group; however, there were no apparent inflammations at the joints at 15 d after drug administration. Moreover, the longer the time of drug administration was, the less apparent the inflammations at the joints will be. The inflammations at the joints were ameliorated evidently on the 30th d in MiR group (p<0.05). Compared with those in control group, the inflammations in model group were increased significantly from the 7th d, with significant differences in the 30th d (p<0.05). The messenger RNA (mRNA) expression levels of interleukin-6 (IL-6), IL-8, and Wnt in MiR group were higher than those in control group, but lower than those in model group (p<0.05), while they were higher in model group than those in control group (p<0.05). The expression level of Wnt protein was decreased in MiR group compared with that in model group (p<0.05), and model group had a prominently elevated expression level of Wnt protein in comparison with control group (p<0.05).

Conclusions: MiR-21 overexpression can repress the expressions of IL-6 and IL-8 and relieve the symptoms of RA by down-regulating the Wnt signal.

MeSH terms

  • Animals
  • Arthritis, Experimental / genetics*
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / therapy
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / therapy
  • Dependovirus / genetics
  • Female
  • Gene Expression Regulation / drug effects
  • Genetic Vectors / administration & dosage*
  • Genetic Vectors / pharmacology
  • Interleukin-6 / genetics
  • Interleukin-8 / genetics
  • MicroRNAs / genetics*
  • Rats
  • Wnt Signaling Pathway / drug effects

Substances

  • Il6 protein, rat
  • Interleukin-6
  • Interleukin-8
  • MicroRNAs
  • mirn21 microRNA, rat