Klotho is a target gene of PPAR-gamma.
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.
Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing, China.
Hong
H
Zhang
Yuanyuan
Y
Li
Yanbo
Y
Fan
Jing
J
Wu
Beilei
B
Zhao
Youfei
Y
Guan
Shu
S
Chien
Nanping
N
Wang
D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D005966:Glucuronidase / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D000090265:Klotho Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D020218:Response Elements; D045162:Thiazolidinediones / Q000494:pharmacology; D014158:Transcription, Genetic
D047495:PPAR gamma; D034741:RNA, Small Interfering; D045162:Thiazolidinediones; D005966:Glucuronidase; D000090265:Klotho Proteins