title: The importin protein karyopherin-β1 regulates the mice fibroblast-like synoviocytes inflammation via facilitating nucleus transportation of STAT3 transcription factor.
abstract: Karyopherin-β1 (KPNB1) which is an adaptor protein which transports several proteins to the nucleus. We study the functions and possible mechanisms of KPNB1 in collagen-induced arthritis (CIA). Western blotting and immunohistochemistry shows the protein expression of KPNB1 is increased in synovial tissue of CIA mice compared with the controls. Double immunofluorescent staining suggests that KPNB1 is expressed in CIA mice fibroblast-like synoviocytes (FLS). Moreover, the expression of KPNB1 in FLS is upregulated in time-dependent manner by IL-1β stimulation. Both immunoprecipitation and immunofluorescent staining assay reveals the interaction between KPNB1 and STAT3 and their translocation from cytoplasm to nucleus in IL-1β-treated FLS. Furthermore, suppression of KPNB1 inhibits IL-1β-induced the nucleus expression of STAT3 in FLS and decreases the expression of IL-6 and MMP-1, leading to attenuation of FLS invasion. Finally, the transport function of KPNB1 is depended on KPNA2. Therefore, we infer that KPNB1 may play a key role in the inflammation process of RA via STAT3 signal transduction pathway.
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Department of Immunology, Medical College, Nantong University, Nantong, 226001, PR China. Electronic address: franksunchi@163.com.
authors.forename: Chi
authors.initials: C
authors.lastname: Sun
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Department of Immunology, Medical College, Nantong University, Nantong, 226001, PR China. Electronic address: yuzhaohui134@163.com.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Orthopedics, Affiliated Hospital of Nantong University, Nantong, 226001, PR China. Electronic address: wyh20151224@yeah.net.
authors.forename: Youhua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Department of Immunology, Medical College, Nantong University, Nantong, 226001, PR China. Electronic address: tao_tao0324@yeah.net.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D028961:beta Karyopherins
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; C094999:Kpnb1 protein, mouse; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D028961:beta Karyopherins; D020781:Matrix Metalloproteinase 1
keywords: Fibroblast-like synoviocytes; IL-1β; KPNB1; Rheumatoid arthritis; STAT3