title: KPNA2 Contributes to the Inflammatory Processes in Synovial Tissue of Patients with Rheumatoid Arthritis and SW982 Cells.
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.
authors.affiliation: 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.
authors.forename: Zhongbing
authors.initials: Z
authors.lastname: Liu
authors.affiliation: 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.|Department of Pathogen Biology, Medical College, Nantong University, Nantong, 226001, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Chi
authors.initials: C
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Ran
authors.initials: R
authors.lastname: Tao
authors.affiliation: 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.
authors.forename: Xinbao
authors.initials: X
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Libin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics, Traditional Chinese Medical Hospital of Nantong City, Nantong, 226001, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Cheng
authors.affiliation: National Glycoengineering Research Center and State Key Laboratory of Microbial Technology, Shandong University, Jinan, 250100, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xiao
authors.affiliation: 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. wangyouhua_nt@163.com.
authors.forename: Youhua
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002460:Cell Line; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D008875:Middle Aged; D034622:RNA Interference; D015398:Signal Transduction; D013583:Synovial Membrane / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation; D028901:alpha Karyopherins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; C490630:KPNA2 protein, human; C498143:RELA protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D028901:alpha Karyopherins; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: P65; SW982; karyopherin-α2 (KPNA2); rheumatoid arthritis (RA); tumor necrosis factor-α (TNFα)