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First published online 10 June 2008
doi: 10.1242/jcs.026633

Journal of Cell Science 121, 2235-2245 (2008)
Published by The Company of Biologists 2008
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Research Article

PPAR{gamma} accelerates cellular senescence by inducing p16INK4{alpha} expression in human diploid fibroblasts

Qini Gan1, Jing Huang1, Rui Zhou1, Jing Niu1, Xiaojun Zhu2, Jing Wang1, Zongyu Zhang1 and Tanjun Tong1,*

1 Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100083, People's Republic of China
2 Cardiovascular Research Institute, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100083, People's Republic of China

* Author for correspondence (e-mail: ttj{at}bjmu.edu.cn)

Accepted 14 April 2008

Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) plays an important role in the inhibition of cell growth by promoting cell-cycle arrest, and PPAR{gamma} activation induces the expression of p16INK4{alpha} (CDKN2A), an important cell-cycle inhibitor that can induce senescence. However, the role of PPAR{gamma} in cellular senescence is unknown. Here, we show that PPAR{gamma} promotes cellular senescence by inducing p16INK4{alpha} expression. We found several indications that PPAR{gamma} accelerates cellular senescence, including enhanced senescence-associated (SA)-β-galactosidase staining, increased G1 arrest and delayed cell growth in human fibroblasts. Western blotting studies demonstrated that PPAR{gamma} activation can upregulate the expression of p16INK4{alpha}. PPAR{gamma} can bind to the p16 promoter and induce its transcription, and, after treatment with a selective PPAR{gamma} agonist, we observed more-robust expression of p16INK4{alpha} in senescent cells than in young cells. In addition, our data indicate that phosphorylation of PPAR{gamma} decreased with increased cell passage. Our results provide a possible molecular mechanism underlying the regulation of cellular senescence.

Key words: PPAR{gamma}, p16INK4{alpha}, Cellular senescence, Fibroblast


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This article has been cited by other articles:


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 Nucleic Acids ResHome page
R. Zhou, L. Han, G. Li, and T. Tong
Senescence delay and repression of p16INK4a by Lsh via recruitment of histone deacetylases in human diploid fibroblasts
Nucleic Acids Res., August 1, 2009; 37(15): 5183 - 5196.
[Abstract] [Full Text] [PDF]


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