High mobility group box 1 induces synoviocyte proliferation in rheumatoid arthritis by activating the signal transducer and activator transcription signal pathway.
Recently, it was discovered that high mobility group box chromosomal protein 1 (HMGB1) acts as a potent pro-inflammatory cytokine that is released into the extracellular milieu. Signal transducer and activator of transcription (STAT) proteins play an important role in cytokine signaling. Some investigators have reported preferential activation of STAT1, and others have reported preferential activation of STAT3 in response to endogenous interleukin-6 (IL-6) in patients with rheumatoid arthritis. Here, we show that expression of the HMGB1 protein is increased in the articular tissues of collagen-induced arthritis (CIA) rats, especially in cytoplasm and extracellular, following synoviocyte proliferation and STAT1 activation. In vitro, recombined human HMGB1 induced RSC-364 cell proliferation, activated STAT1 phosphorylation, increased the expression of cyclin D1 and CDK4 protein, and decreased the expression of p21 protein. In summary, our study suggests that HMGB1 plays an important role of cytokine in the pathogenesis of RA, which possibly induces synovial cell proliferation by activating the STAT1 signal pathway.
Department of Rheumatology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Hui-Fang
HF
Guo
Shu-Xia
SX
Liu
Yu-Jun
YJ
Zhang
Qing-Juan
QJ
Liu
Jun
J
Hao
Li-Xia
LX
Gao
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D002460:Cell Line; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology*; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051381:Rats; D017208:Rats, Wistar; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013583:Synovial Membrane / Q000473:pathology*
C530106:Ccnd1 protein, rat; D024243:HMGB1 Protein; D050794:STAT1 Transcription Factor; C494081:Stat1 protein, rat; D019938:Cyclin D1; C495903:Cdk4 protein, rat; D051358:Cyclin-Dependent Kinase 4