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.