Kruppel-like factor KLF9 regulates PPARγ transactivation at the middle stage of adipogenesis
Kruppel-like factor KLF9 regulates PPARγ transactivation at the middle stage of adipogenesis
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DOI：
10.1038/cdd.2010.100
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发表时间：
2011-02-01
影响因子：
12.4
通讯作者：
Wu, J-R
中科院分区：
文献类型：
--
作者：
Pei, H.;Yao, Y.;Wu, J-R
Kruppel样因子（KLFs）是一类锌指转录因子，参与多种生理过程的调控。在这些研究中，KLF 9的特征在于其在脂肪形成中的作用。在3 T3-L1脂肪细胞分化中期，KLF 9的表达明显上调，RNAi抑制KLF 9的表达可抑制3 T3-L1脂肪细胞的成脂能力。使用启动子缺失和突变分析，我们确定了两个KLF 9的结合位点内的0.6 kb区域的PPAR γ 2近端启动子，表明KLF 9与PPAR γ 2启动子相互作用。此外，我们发现KLF 9可以通过直接与C/EBP α相互作用而协同激活PPAR γ 2启动子。此外，过表达的PPARgamma 2挽救了由KLF 9敲低诱导的脂肪细胞分化的损伤，这支持PPARgamma 2是KLF 9的下游靶点。总的来说，我们的研究结果表明，KLF 9作为一个关键的前脂肪形成的转录因子，通过调节PPAR γ 2的表达与C/EBP α在脂肪形成的中期阶段。Cell Death and Differentiation（2011）18，315-327; doi：10.1038/cdd.2010.100; 2010年8月20日在线发表
Kruppel-like factors (KLFs) as a family of zinc-finger transcription factors involve in the regulation of many physiological processes. In these studies, KLF9 was characterized for its role in adipogenesis. The expression of KLF9 was markedly upregulated during the middle stage of 3T3-L1 adipocyte differentiation, and inhibition of KLF9 by RNAi impaired adipogenesis. Using promoter deletion and mutation analysis, we identified two KLF9-binding sites within the 0.6-kb region of the PPAR gamma 2 proximal promoter, indicating that KLF9 interacts with the PPAR gamma 2 promoter. Furthermore, we found that KLF9 could synergistically activate PPAR gamma 2 promoter by directly interacting with C/EBP alpha. In addition, overexpression of PPAR gamma 2 rescued the impairment of adipocyte differentiation induced by KLF9 knockdown, which supports that PPAR gamma 2 is a downstream target of KLF9. Collectively, our results indicate KLF9 as a key pro-adipogenic transcription factor through regulation of PPAR gamma 2 expression with C/EBP alpha at the middle stage of adipogenesis. Cell Death and Differentiation (2011) 18, 315-327; doi: 10.1038/cdd.2010.100; published online 20 August 2010