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学科主题: 基础医学
题名:
PPAR gamma accelerates cellular senescence by inducing p16(INK4 alpha) expression in human diploid fibroblasts
作者: Gan, Qini1; Huang, Jing1; Zhou, Rui1; Niu, Jing1; Zhu, Xiaojun2; Wang, Jing1; Zhang, Zongyu1; Tong, Tanjun1
关键词: PPAR gamma ; p16(INK4 alpha) ; cellular senescence ; fibroblast
刊名: JOURNAL OF CELL SCIENCE
发表日期: 2008-07-01
DOI: 10.1242/jcs.026633
卷: 121, 期:13, 页:2235-2245
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology
研究领域[WOS]: Cell Biology
关键词[WOS]: ACTIVATED RECEPTOR-GAMMA ; HUMAN BREAST-CANCER ; P16(INK4A) EXPRESSION ; TUMOR-SUPPRESSOR ; TERMINAL DIFFERENTIATION ; GENE-EXPRESSION ; GROWTH-FACTOR ; LUNG-CANCER ; IN-VITRO ; CELLS
英文摘要:

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 p16(INK4 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 p16(INK4 alpha) expression. We found several indications that PPAR gamma accelerates cellular senescence, including enhanced senescence-associated ( SA)-beta-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 p16(INK4 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 p16(INK4 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.

语种: 英语
WOS记录号: WOS:000256879900015
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54814
Appears in Collections:基础医学院_北京大学衰老研究中心_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Res Ctr Aging, Dept Biochem & Mol Biol, Beijing 100083, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Cardiovasc Res Inst, Beijing 100083, Peoples R China

Recommended Citation:
Gan, Qini,Huang, Jing,Zhou, Rui,et al. PPAR gamma accelerates cellular senescence by inducing p16(INK4 alpha) expression in human diploid fibroblasts[J]. JOURNAL OF CELL SCIENCE,2008,121(13):2235-2245.
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