Open AccessKlotho is a target gene of PPAR-γ
Author(s) -
Hong Zhang,
Yuanyuan Li,
Yanbo Fan,
Jing Wu,
Beilei Zhao,
Youfei Guan,
Shu Chien,
Nanping Wang
Publication year - 2008
Publication title -
kidney international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.499
H-Index - 276
eISSN - 1523-1755
pISSN - 0085-2538
DOI - 10.1038/ki.2008.244
Subject(s) - klotho , peroxisome proliferator activated receptor , gene silencing , gene expression , reporter gene , biology , nuclear receptor , regulation of gene expression , transfection , microbiology and biotechnology , gene , messenger rna , receptor , cancer research , endocrinology , kidney , transcription factor , genetics
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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