学科主题基础医学
PPAR gamma accelerates cellular senescence by inducing p16(INK4 alpha) expression in human diploid fibroblasts
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
2008-07-01
DOI10.1242/jcs.026633
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
引用统计
被引频次:33[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54814
专题北京大学基础医学院_北京大学衰老研究中心
北京大学基础医学院
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
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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.
APA Gan, Qini.,Huang, Jing.,Zhou, Rui.,Niu, Jing.,Zhu, Xiaojun.,...&Tong, Tanjun.(2008).PPAR gamma accelerates cellular senescence by inducing p16(INK4 alpha) expression in human diploid fibroblasts.JOURNAL OF CELL SCIENCE,121(13),2235-2245.
MLA Gan, Qini,et al."PPAR gamma accelerates cellular senescence by inducing p16(INK4 alpha) expression in human diploid fibroblasts".JOURNAL OF CELL SCIENCE 121.13(2008):2235-2245.
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