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Eur Rev Med Pharmacol Sci ; 23(19): 8186-8193, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31646548

RESUMO

OBJECTIVE: The aim of this study was to investigate whether microRNA-421 could participate in the proliferative, migratory and inflammatory changes of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis by targeting SPRY1. PATIENTS AND METHODS: The expressions of microRNA-421 and SPRY1 in synovial tissues and FLS were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. The binding condition between microRNA-421 and SPRY1 was verified by the Dual-Luciferase reporter gene assay. MicroRNA-421 mimics and inhibitor were constructed and transfected. The levels of extracellular interleukin-1 (IL-1), IL-6, and COX2 in FLS after microRNA-421 mimics or inhibitor transfection were detected by enzyme-linked immunosorbent assay (ELISA). The regulatory effect of microRNA-421 on the proliferation and migration of FLS was detected using cell counting kit-8 (CCK-8) and transwell assay, respectively. Furthermore, collagen-induced RA mouse model was constructed to confirm the specific effect of microRNA-421 on regulating RA development. RESULTS: MicroRNA-421 was highly expressed in the synovial tissues of RA patients. SPRY1 expression in FLS was negatively regulated by microRNA-421. Moreover, the overexpression of microRNA-421 significantly promoted proliferative, invasive potentials and inflammatory response of FLS. In vivo, RA mouse model indicated that downregulated microRNA-421 and upregulated SPRY1 were observed in mice injected with cortisone and microRNA-421 inhibitor when compared with those of controls. CONCLUSIONS: MicroRNA-421 promotes the inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis by downregulating the SPRY1 expression.


Assuntos
Artrite Reumatoide/metabolismo , Inflamação/metabolismo , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Fosfoproteínas/metabolismo , Sinoviócitos/metabolismo , Animais , Western Blotting , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos DBA , Reação em Cadeia da Polimerase em Tempo Real
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