title: 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.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
authors.forename: Jiayin
authors.initials: J
authors.lastname: Lu
authors.forename: Mei
authors.initials: M
authors.lastname: Yan
authors.forename: Yuzhong
authors.initials: Y
authors.lastname: Wang
authors.forename: Junmei
authors.initials: J
authors.lastname: Zhang
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.forename: Fa-Fa
authors.initials: FF
authors.lastname: Tian
authors.forename: Wenbin
authors.initials: W
authors.lastname: Zhou
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D055815:Young Adult
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D011950:Receptors, Cholinergic; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
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