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MicroRNA-21 Promotes Proliferation of Fibroblast-Like Synoviocytes through Mediation of NF-κB Nuclear Translocation in a Rat Model of Collagen-Induced Rheumatoid Arthritis.

Abstract
MicroRNA-21 (miR-21) is overexpressed in patients with rheumatoid arthritis (RA). This study was designed to investigate the effect and mechanism of miR-21 on cell proliferation in fibroblast-like synoviocytes (FLS) of RA. FLS were primary-cultured from a rat RA model. RA-FLS and normal FLS were infected with lentivirus (anti-miR-21 or pro-miR-21) for overexpression or downregulation of miR-21, respectively. The effects of miR-21 overexpression or inhibition on nucleoprotein NF-κB levels and FLS cell proliferation were evaluated by western blotting and MTT assays. The effects of an inhibitor of NF-κB nuclear translocation (BAY 11-7082) were also evaluated. The results showed that the levels of miR-21 and nucleoprotein NF-κB were increased in FLS of RA model rats compared to the control group. Downregulation of miR-21 in RA FLS led to a significant decrease in nucleoprotein NF-κB levels and cell proliferation rates compared to the antinegative control (NC) group. However, miR-21 overexpression in normal FLS resulted in a significant increase of nucleoprotein NF-κB levels and cell proliferation rates compared to the pro-NC group. The effects of miR-21 overexpression were reversed by BAY 11-7082. We concluded that upregulated miR-21 in FLS in RA model rats may promote cell proliferation by facilitating NF-κB nuclear translocation, thus affecting the NF-κB pathway.
AuthorsYing Chen, Pei-Feng Xian, Lu Yang, Sheng-Xu Wang
JournalBioMed research international (Biomed Res Int) Vol. 2016 Pg. 9279078 ( 2016) ISSN: 2314-6141 [Electronic] United States
PMID27429986 (Publication Type: Journal Article)
Chemical References
  • MicroRNAs
  • NF-kappa B
  • mirn21 microRNA, rat
Topics
  • Animals
  • Arthritis, Experimental (genetics, pathology)
  • Arthritis, Rheumatoid (genetics, pathology)
  • Cell Nucleus (metabolism)
  • Cell Proliferation
  • Cell Survival
  • Disease Models, Animal
  • Down-Regulation (genetics)
  • Fibroblasts (metabolism, pathology)
  • Male
  • MicroRNAs (genetics, metabolism)
  • NF-kappa B (metabolism)
  • Protein Transport
  • Rats, Wistar
  • Synoviocytes (metabolism, pathology)

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