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1: Kidney Int. 2008 Sep;74(6):732-9. Epub 2008 Jun 11.
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Klotho is a target gene of PPAR-gamma.

Zhang H, Li Y, Fan Y, Wu J, Zhao B, Guan Y, Chien S, Wang N.

Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing, China.

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-gamma (PPAR-gamma). The PPAR-gamma agonists thiazolidinediones increased both klotho mRNA and protein expression in HEK293 cells and several renal epithelial cell lines. The induction was blocked by PPAR-gamma antagonists or small-interfering RNA-mediated gene silencing of PPAR-gamma, suggesting a PPAR-gamma-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-gamma increased klotho expression in mouse kidneys while renal klotho expression was attenuated in mice treated with PPAR-gamma antagonists. These results demonstrate that klotho is a target gene of PPAR-gamma.

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PMID: 18547997 [PubMed - in process]