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HMGB1 mediates IFN‐γ‐induced cell proliferation in MMC cells through regulation of cyclin D1/CDK4/p16 pathway
Author(s) -
Feng Xiaojuan,
Hao Jun,
Liu Qingjuan,
Yang Lin,
Lv Xin,
Zhang Yujun,
Xing Lingling,
Xu Ning,
Liu Shuxia
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24071
Subject(s) - cyclin d1 , hmgb1 , cell growth , proliferating cell nuclear antigen , cyclin d , lupus nephritis , cell cycle , cancer research , mesangial cell , cell , cyclin , biology , microbiology and biotechnology , cyclin a , interferon , immunology , medicine , endocrinology , kidney , biochemistry , inflammation , disease
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. J. Cell. Biochem. 113: 2009–2019, 2012. © 2012 Wiley Periodicals, Inc.