title: MiR-451 inhibits synovial fibroblasts proliferation and inflammatory cytokines secretion in rheumatoid arthritis through mediating p38MAPK signaling pathway.
abstract: Rheumatoid arthritis is an autoimmune disease characterized as joint synovial inflammation. MicroRNA is a group of small noncoding RNA molecules discovered in recent years that can posttranscriptional regulate mRNA expression and involved in a variety processes of immune cell activation and differentiation. There is still lack of study about the role of miR-451 in rheumatoid arthritis. Synovial fibroblasts isolated from rheumatoid arthritis patients were cultured in vitro. Chemical synthesized miR-451 was lipo-transfected, real-time RT-PCR was applied to detect miR-451 expression level, and MTT method was used to detect the effect of miR-451 on synovial fibroblasts proliferation. Enzyme-linked immunosorbent assay was used to detect tumor necrosis factor TNF-α, IL-1β, and IL-6 level in the supernatant. Western blot was applied to test target protein p38 MAPK expression level. Our study found that synovial fibroblasts expressed higher miR-451 mRNA level in miR-451 treatment group. MiR-451 treatment significantly decreased cell proliferation ability (P < 0.05). Compared with the control, p38 MAPK protein expression reduced obviously in the miR-451 treatment group (P < 0.05). MiR-451 transfected synovial fibroblasts secreted lower levels of TNF-α (198 ± 12 pg/ml vs 124 ± 13 pg/ml, P < 0.01), IL-1β (352 ± 43 pg/ml vs 165 ± 87 pg/ml, P < 0.01), and IL-6 (487 ± 84 pg/ml vs 257 ± 92 pg/ml, P < 0.01). The results proved that miR-451 can down-regulate p38 MAPK protein expression, and reduce synovial fibroblasts proliferation and cytokine expression level.
authors.affiliation: Department of Orthopedics, Xinhua Hospital (Chongming), Shanghai Jiaotong University Shanghai 202150, China.
authors.forename: Zhan-Chao
authors.initials: ZC
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Xinhua Hospital, Shanghai Jiaotong University Shanghai 200092, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Orthopedics, Xinhua Hospital (Chongming), Shanghai Jiaotong University Shanghai 202150, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, Xinhua Hospital (Chongming), Shanghai Jiaotong University Shanghai 202150, China.
authors.forename: Si-Ming
authors.initials: SM
authors.lastname: Yu
authors.affiliation: Department of Orthopedics, Xinhua Hospital (Chongming), Shanghai Jiaotong University Shanghai 202150, China.
authors.forename: Yu-Lun
authors.initials: YL
authors.lastname: Mao
authors.affiliation: Department of Orthopedics, Xinhua Hospital (Chongming), Shanghai Jiaotong University Shanghai 202150, China.
authors.forename: Hao-Jie
authors.initials: HJ
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Xinhua Hospital (Chongming), Shanghai Jiaotong University Shanghai 202150, China.
authors.forename: Ping-Chao
authors.initials: PC
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Changzheng Hospital, Second Military Medical University Shanghai 200061, China.
authors.forename: Wang-Jun
authors.initials: WJ
authors.lastname: Yan
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000473:pathology*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013583:Synovial Membrane; D014162:Transfection
chemical_list: D016207:Cytokines; C531201:MIRN451 microRNA, human; D035683:MicroRNAs
keywords: cell proliferation; miR-451; rheumatoid arthritis; synovial fibroblast
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