Krox20通过依赖C/EBPβ和不依赖C/EBPβ的机制刺激脂肪生成。
Krox20 stimulates adipogenesis via C/EBPbeta-dependent and -independent mechanisms.
作者信息
Chen Zhu, Torrens Javier I, Anand Ashim, Spiegelman Bruce M, Friedman Jeffrey M
机构信息
Laboratory of Molecular Genetics, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
出版信息
Cell Metab. 2005 Feb;1(2):93-106. doi: 10.1016/j.cmet.2004.12.009.
Krox20 is a zinc finger-containing transcription factor that is abundantly expressed in adipose tissue. However, its role in fat cell differentiation has not been established. In cultured 3T3-L1 cells, Krox20 is rapidly induced by serum stimulation. Overexpression of Krox20 in both 3T3-L1 preadipocytes and multipotent NIH3T3 cells promotes adipogenesis in a hormone-dependent manner. Conversely, RNAi-mediated loss of Krox20 function reduced adipogenesis in 3T3-L1 cells. Ectopic expression of Krox20 can transactivate the C/EBPbeta promoter and increase C/EBPbeta gene expression in 3T3-L1 preadipocytes. RNAi-mediated knockdown of C/EPBbeta diminished Krox20's proadipogenic effect. Finally, coexpression of Krox20 and C/EBPbeta in naive NIH3T3 cells resulted in the pronounced induction of a fully differentiated adipocyte phenotype, an effect previously observed only with PPARgamma. These data indicate that Krox20 is necessary for adipogenesis and that, when overexpressed, Krox20 potently stimulates adipogenesis via C/EBPbeta-dependent and -independent mechanisms.
Krox20是一种含锌指结构的转录因子，在脂肪组织中大量表达。然而，其在脂肪细胞分化中的作用尚未明确。在培养的3T3-L1细胞中，血清刺激可迅速诱导Krox20表达。在3T3-L1前脂肪细胞和多能NIH3T3细胞中过表达Krox20可通过激素依赖的方式促进脂肪生成。相反，RNA干扰介导的Krox20功能缺失会降低3T3-L1细胞中的脂肪生成。Krox20的异位表达可反式激活C/EBPβ启动子，并增加3T3-L1前脂肪细胞中C/EBPβ基因的表达。RNA干扰介导的C/EPBβ敲低可减弱Krox20的促脂肪生成作用。最后，在未分化的NIH3T3细胞中共表达Krox20和C/EBPβ可显著诱导完全分化的脂肪细胞表型，这种效应之前仅在过氧化物酶体增殖物激活受体γ（PPARγ）存在时观察到。这些数据表明，Krox20是脂肪生成所必需的，并且过表达时，Krox20可通过依赖和不依赖C/EBPβ的机制有效刺激脂肪生成。
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