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KPNA2 Contributes to the Inflammatory Processes in Synovial Tissue of Patients with Rheumatoid Arthritis and SW982 Cells

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Abstract

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.

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Acknowledgments

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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    Authors and Affiliations

    1. Department of Orthopaedics, Affiliated Hospital of Nantong University, and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu Province, China

      Zhongbing Liu, Dongmei Zhang, Chi Sun, Ran Tao, Xinbao Xu, Libin Xu & Youhua Wang

    2. Department of Pathogen Biology, Medical College, Nantong University, Nantong, 226001, China

      Dongmei Zhang

    3. Department of Orthopaedics, Traditional Chinese Medical Hospital of Nantong City, Nantong, 226001, China

      Hongbing Cheng

    4. National Glycoengineering Research Center and State Key Laboratory of Microbial Technology, Shandong University, Jinan, 250100, China

      Min Xiao

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    1. Zhongbing Liu
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    Correspondence to Youhua Wang.

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    Zhongbing Liu and Dongmei Zhang contributed equally to this work.

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    Liu, Z., Zhang, D., Sun, C. et al. KPNA2 Contributes to the Inflammatory Processes in Synovial Tissue of Patients with Rheumatoid Arthritis and SW982 Cells. Inflammation 38, 2224–2234 (2015). https://doi.org/10.1007/s10753-015-0205-2

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