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.

miR‑137 decreases proliferation, migration and invasion in rheumatoid arthritis fibroblast‑like synoviocytes

“…An increasing number of studies have indicated that the aberrant expression of miRNAs was involved in RA progression through regulating cell proliferation, migration and invasion (8,9). For example, a recent study reported that increased miR-21 expression in FLS in RA model rats promoted cell proliferation by facilitating the nuclear translocation of NF-κB (17). Another recent study demonstrated that decreased miR-221 expression led to a significant reduction in the expression of pro-inflammatory cytokines, and inhibited FLS migration and invasion through the inhibition of vascular endothelial growth factor, matrix metalloproteinase (MMP)-3 and MMP-9 expression (22).…”

“…Cell culture and transfection. FLSs were obtained from the synovial tissues of RA and normal control rats as described previously (17). Briefly, synovial tissues were obtained and were cut into blocks of 1x1x1 mm in Dulbecco's modified Eagle's medium (DMEM; Gibco; Thermo Fisher Scientific, Inc., Waltham, MA, USA) under sterile conditions.…”

(5R)-5-hydroxytriptolide (LLDT-8) prevents collagen-induced arthritis through OPG/RANK/RANKL signaling in a rat model of rheumatoid arthritis

“…CIA was used to mimic RA, and has previously been confirmed as a valid model of this (18). Type II collagen was obtained from the Tauto Biotech Co., Ltd, (Shanghai, China) and dissolved in 0.1 M acetic acid.…”

MiR‐1193 represses the proliferation and induces the apoptosis of interleukin‐1β‐treated fibroblast‐like synoviocytes via targeting JAK3

“…[41][42][43] For instance, miR-126 was inhibited in patients and influenced the proliferation and apoptosis of RA synovial fibroblasts by targeting P1K3R2 via the P13K-AKT pathway, indicating that its high expression might be a potential therapy for RA. 44,45 Moreover, the promoting effect of miR-21 on the proliferation of fibroblast-like synoviocytes in collagen-induced RA via the nuclear factor-κB pathway was proven in the study of Chen et al 46 Accumulated evidence proves that miRNAs can repress the translation of targeted mRNAs in humans and other animals. 47,48 MiR-1193 was screened and verified as the upstream regulatory miRNA of JAK3 in our study ac- and to a minor degree of JAK2, was found to be effective in the treatment of RA.…”