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- Title
Klotho is a target gene of PPAR-γ.
- Authors
Hong Zhang; Yuanyuan Li; Yanbo Fan; Jing Wu; Beilei Zhao; Youfei Guan; Shu Chien; Nanping Wang
- Abstract
Klotho is an anti-aging gene whose expression is regulated by many stimuli. Here we examined the transcriptional regulation of the klotho gene by peroxisome proliferator-activated receptor-γ (PPAR-γ). The PPAR-γ agonists thiazolidinediones increased both klotho mRNA and protein expression in HEK293 cells and several renal epithelial cell lines. The induction was blocked by PPAR-γ antagonists or small-interfering RNA-mediated gene silencing of PPAR-γ, suggesting a PPAR-γ-dependent mechanism. Chromatin immuno-precipitation and gel shift assays found a noncanonical PPAR-responsive element within the 5′-flanking region of the human klotho gene with promoter–reporter assays further confirming transcriptional functionality. Moreover, thiazolidinediones or adenovirus-mediated overexpression of PPAR-γ increased klotho expression in mouse kidneys while renal klotho expression was attenuated in mice treated with PPAR-γ antagonists. These results demonstrate that klotho is a target gene of PPAR-γ.Kidney International (2008) 74, 732–739; doi:10.1038/ki.2008.244; published online 11 June 2008
- Subjects
GENES; GENE expression; CELL lines; GENE silencing; LABORATORY rats; KIDNEYS
- Publication
Kidney International, 2008, Vol 74, Issue 6, p732
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.2008.244