KPNA2 Contributes to the Inflammatory Processes in Synovial Tissue of Patients with Rheumatoid Arthritis and SW982 Cells
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Karyopherin-α2 (KPNA2) functions as an adaptor that transports several proteins to the nucleus. We investigated the function and possible mechanisms of KPNA2 involved in rheumatoid arthritis (RA). Western blotting and immunohistochemistry showed the protein expression of KPNA2 increased in synovial tissue of RA patients compared with the healthy controls. Double immunofluorescent staining indicated that KPNA2 co-localized with T cells, macrophage-like synoviocytes, fibroblast-like synoviocytes, and neutrophils in synovial tissue of RA patients. Moreover, the expression of KPNA2 in SW982 cells was increased in a time-dependent manner in response to TNFα stimulation. Both Western blotting and immunofluorescent staining assay revealed the co-localization of KPNA2 and P65 and their translocation from cytoplasma in TNFα-treated SW982 cells. Furthermore, knocking down the expression of KPNA2 by siRNA inhibited TNFα-induced expression of IL-6, MMP-1, and MMP-13 and, more importantly, decreased the P65 phosphorylation in SW982 cells. We therefore suggested that KPNA2 may play a key role in the inflammation process of RA via NF-κB P65 signal transduction pathway.
KEY WORDSkaryopherin-α2 (KPNA2) rheumatoid arthritis (RA) SW982 tumor necrosis factor-α (TNFα) P65
This work was supported by Postgraduate Technology Innovation Project of Nantong University (YKS14004), Clinical Medicine Special Funds of Jiangsu Province (BL2014059), National Basic Research Program of China (973 Program, No. 2012CB822104), National Natural Science Foundation of China (31170766), National Natural Science Foundation of China (81171140), Key Project Natural Science Foundation of Jiangsu University and College (No. 11KJA310002), Nantong City Social Development Projects funds (HS2012032), and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
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