Sam68 Promotes Invasion, Migration, and Proliferation of Fibroblast-like Synoviocytes by Enhancing the NF- κB/P65 Pathway in Rheumatoid Arthritis

In this study, we analyzed the effect and possible mechanisms of Sam68 in rheumatoid arthritis (RA). By western blot analysis and immunohistochemistry, we found that the expression of Sam68 in synovial tissue of RA patients was increased compared with the cont rol group. Immunoflourescent staining demonstrated that Sam68 co-localized with fibroblast-like synoviocytes (FLS) of RA patients. Additionally, the expression of Sam68 in FLS was increased by tumor necrosis factor (TNF)-α stimulation, in a time-dependent manner. Upon TNF-α treatment, Sam68 transl ocated from the cytoplasm to the nucleus where it interacted with the p65 subunit of NF-κB, as examined by immunoprecipitation and immunofluorescent staining assay. Furthermore, inhibiting the expression of Sam68 by siRNA significantly suppressed the TNF-α-induced expression of interleukin (IL)-6, and matrix metalloproteinase (MMP)-1, reduced the proliferation, migration, and invasion, and markedly decreased the phosphorylation of P65 and IκBα in FLS. Collectively, our findings suggested that Sam68 contributed to the production of inflammatory cytokines, proliferation, migration, and invas ion of RA FLS through the NF-κB P65 signal transduction pathway and underscored the importance of Sam68 in the inflammation process of RA.
Source: Inflammation - Category: Allergy & Immunology Source Type: research