Altered expression of miR-146a in myasthenia gravis

Abstract

The purpose of this study was to analyze the expression of miR-146a in PBMCs obtained from patients with myasthenia gravis (MG) and healthy controls and to investigate the effect of the inhibition of miR-146a on the activation of AchR specific B cells obtained from mice. The expression of miR-146a levels in PBMCs obtained from patients with MG and healthy controls were determined by qRT-PCR. MiR-146a's complementary fragment, AntagomiR-146a, was synthesized as inhibitor, and the nonfunctional fragment, which has similar construction to AntagomiR-146a, was synthesized as negative control inhibitor. The expression of miR-146a, CD40, CD80 and CD86 on AchR specific B cells were analyzed by qRT-PCR and flow cytometry. Western blotting was used to detect the expression of TLR4, NF-κB and Bcl-2 .The expression of miRNA-146a in PBMCs obtained from patients with MG was significantly upregulated compared to healthy controls (P<0.01). Transfection with miR-146a inhibitor dramatically decreased expression of miR-146a, CD40, CD80, TLR4 and NF-κB on AchR specific B cells compared to mock transfected cells. We conclude that abnormal expression/regulation of miR-146a may play an important role in the regulation of AchR specific B cells and contribute to the pathogenesis of MG.

Keywords: AchR; B cell; EAMG; IL-1 receptor associated kinase 1; IRAK-1; MG; Myasthenia gravis; NF-κB; NMJ; PBMCs; RA; SLE; TLR4; TNF receptor associated factor 6; TRAF-6; Toll like receptor 4; acetylcholine receptor; experimental autoimmune myasthenia gravis; miR-146a; miRNA-146a; microRNA-146a; myasthenia gravis; neuromuscular junction; nuclear factor-κB; peripheral blood mononuclear cells; rheumatoid arthritis; systemic lupus erythematosus.