Klotho is a target gene of PPAR-γ

Hong Zhang; Yuanyuan Li; Yanbo Fan; Jing Wu; Beilei Zhao; Youfei Guan; Shu Chien; Nanping Wang

doi:10.1038/ki.2008.244

Klotho is a target gene of PPAR-γ

Hong Zhang
, Yuanyuan Li
, Yanbo Fan
, Jing Wu
, Beilei Zhao
, Youfei Guan
, Shu Chien
, Nanping Wang^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

162 Scopus citations

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.

Original language	English
Pages (from-to)	732-739
Number of pages	8
Journal	Kidney International
Volume	74
Issue number	6
DOIs	https://doi.org/10.1038/ki.2008.244
State	Published - Sep 2008
Externally published	Yes

Keywords

Diabetic nephropathy
Gene expression
Transcription factor

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ki.2008.244

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title = "Klotho is a target gene of PPAR-γ",

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.",

keywords = "Diabetic nephropathy, Gene expression, Transcription factor",

author = "Hong Zhang and Yuanyuan Li and Yanbo Fan and Jing Wu and Beilei Zhao and Youfei Guan and Shu Chien and Nanping Wang",

year = "2008",

month = sep,

doi = "10.1038/ki.2008.244",

language = "英语",

volume = "74",

pages = "732--739",

journal = "Kidney International",

issn = "0085-2538",

publisher = "Elsevier B.V.",

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}

TY - JOUR

T1 - Klotho is a target gene of PPAR-γ

AU - Zhang, Hong

AU - Li, Yuanyuan

AU - Fan, Yanbo

AU - Wu, Jing

AU - Zhao, Beilei

AU - Guan, Youfei

AU - Chien, Shu

AU - Wang, Nanping

PY - 2008/9

Y1 - 2008/9

N2 - 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.

AB - 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.

KW - Diabetic nephropathy

KW - Gene expression

KW - Transcription factor

UR - https://www.scopus.com/pages/publications/50849091263

U2 - 10.1038/ki.2008.244

DO - 10.1038/ki.2008.244

M3 - 文章

C2 - 18547997

AN - SCOPUS:50849091263

SN - 0085-2538

VL - 74

SP - 732

EP - 739

JO - Kidney International

JF - Kidney International

IS - 6

ER -

Klotho is a target gene of PPAR-γ

Abstract

Keywords

UN SDGs

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