Klotho is a target gene of PPAR-gamma.
Klotho is a target gene of PPAR-gamma.
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DOI：
10.1038/ki.2008.244
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发表时间：
2008-09
影响因子：
19.6
通讯作者：
Hong Zhang;Yuan-yuan Li;Yanbo Fan;Jing Wu;Beilei Zhao;Y. Guan;S. Chien;Nanping Wang
中科院分区：
文献类型：
--
作者：
Hong Zhang;Yuan-yuan Li;Yanbo Fan;Jing Wu;Beilei Zhao;Y. Guan;S. Chien;Nanping Wang
Klotho是一种抗衰老基因，其表达受多种刺激调节。在这里，我们研究了过氧化物酶体增殖物激活受体-γ（过氧化物酶体增殖物激活受体-γ）的klotho基因的转录调控。在HEK 293细胞和几种肾上皮细胞系中，PPAR-γ激动剂噻唑烷二酮类可增加klotho mRNA和蛋白表达。这种诱导作用可被PPAR-γ拮抗剂或小干扰RNA介导的PPAR-γ基因沉默所阻断，表明其机制为PPAR-γ依赖性。染色质免疫沉淀和凝胶迁移试验发现，在人klotho基因的5′-侧翼区域内存在一个非典型的PPAR-responsive元件，启动子-报告基因试验进一步证实了转录功能。此外，噻唑烷二酮类或腺病毒介导的PPAR-γ过表达增加了小鼠肾脏中的klotho表达，而用PPAR-γ拮抗剂处理的小鼠肾脏中的klotho表达减弱。这些结果表明klotho是PPAR-γ的靶基因。
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.