Kruppel-like transcription factor KLF5 is a key regulator of adipocyte differentiation
Kruppel-like transcription factor KLF5 is a key regulator of adipocyte differentiation
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DOI：
10.1016/j.cmet.2004.11.005
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发表时间：
2005-01-01
期刊：
影响因子：
29
通讯作者：
Nagai, R
中科院分区：
文献类型：
--
作者：
Oishi, Y;Manabe, I;Nagai, R
Kruppel-like factor5(KLF5)是一种锌指转录因子，在心血管疾病的发病机制中起着关键作用。在这里，我们发现：新生的杂合子KLF5基因敲除小鼠在白色脂肪组织发育方面表现出明显的缺陷，这表明KLF5也是脂肪形成所必需的。在3T3-L1前脂肪细胞中，KLF5在分化早期被诱导表达，随后是PPARγ(2)的表达。显性负KLF5的结构性过表达抑制脂肪细胞的分化，而野生型KLF5的过表达即使在没有激素刺激的情况下也能诱导分化。此外，从KLF5(+/-)小鼠获得的胚胎成纤维细胞显示脂肪细胞分化明显减弱，证实了KLF5在脂肪细胞分化中的关键作用。KLF5的表达受C/EBPβ和Delta的诱导。KLF5进而与C/EBPβ/Delta协同作用，激活PPARγ(2)启动子。这项研究确定KLF5是控制脂肪细胞分化的转录因子网络的关键组成部分。
Kruppel-like factor 5 (KLF5) is a zinc-finger transcription factor known to play a pivotal role in the pathogenesis of cardiovascular disease. Here, we show: that neonatal heterozygous KLF5 knockout mice exhibit a marked deficiency in white adipose tissue development, suggesting that KLF5 is also required for adipogenesis. In 3T3-L1 preadipocytes, KLF5 expression was induced at an early stage of differentiation, and this was followed by expression of PPAR gamma(2). Constitutive overexpression of dominant-negative KLF5 inhibited adipocyte differentiation, whereas overexpression of wild-type KLF5 induced differentiation even without hormonal stimulation. Moreover, embryonic fibroblasts obtained from KLF5(+/-) mice showed much attenuated adipocyte differentiation, confirming the key role played by KLF5 in adipocyte differentiation. KLF5 expression is induced by C/EBP beta and delta. KLF5, in turn, acts in concert with C/EBP beta/delta to activate the PPAR gamma(2) promoter. This study establishes KLF5 as a key component of the transcription factor network controlling adipocyte differentiation.