title: HMGB1 mediates IFN-γ-induced cell proliferation in MMC cells through regulation of cyclin D1/CDK4/p16 pathway.
abstract: Previous studies have revealed the elevated serum levels of High-mobility group box-1(HMGB1) and the interferon-γ (IFN-γ)-induced proliferation of renal mesangial cells in patients or experimental animals with systemic lupus erythematosus (SLE). However, it is still not elucidated whether HMGB1 involves in the pathogenesis of lupus nephritis (LN) and mediates IFN-γ-induced mesangial cell proliferation. Therefore, in the present study we demonstrated HMGB1 mRNA and protein levels were increased in the glomeruli of LN patients and BXSB mice. HMGB1 increased the proliferation index of mouse mesangial cells (MMC) that was accompanied with the up-regulation of cyclin D1, CDK4 and the down-regulation of p16, subsequently promoting the transition from the G0/G1 to S stage. Inhibition of HMGB1 by a specific short hairpin RNA vector prevented cyclin D1/CDK4/p16 up-regulation and attenuated IFN-γ-induced MMC cell proliferation and PCNA (proliferating cell nuclear antigen, PCNA) expression. These findings indicate that HMGB1 mediates IFN-γ-induced cell proliferation in MMC cells through regulation of cyclin D1/CDK4/p16 pathway and promoting the cell cycle transition from G1 to S stage.
authors.affiliation: Department of Pathology, Hebei Medical University, and Department of Nephrology, the 2nd Hospital of Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Feng
authors.forename: Jun
authors.initials: J
authors.lastname: Hao
authors.forename: Qingjuan
authors.initials: Q
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Xin
authors.initials: X
authors.lastname: Lv
authors.forename: Yujun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lingling
authors.initials: L
authors.lastname: Xing
authors.forename: Ning
authors.initials: N
authors.lastname: Xu
authors.forename: Shuxia
authors.initials: S
authors.lastname: Liu
mesh_terms: D000328:Adult; D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D005260:Female; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism; D008181:Lupus Nephritis / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D050527:Mesangial Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D055815:Young Adult
chemical_list: D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D024243:HMGB1 Protein; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019938:Cyclin D1; D007371:Interferon-gamma; C495902:Cdk4 protein, mouse; D051358:Cyclin-Dependent Kinase 4