Dual roles for the notch target gene Hes-1 in the differentiation of 3T3-L1 preadipocytes
Dual roles for the notch target gene Hes-1 in the differentiation of 3T3-L1 preadipocytes
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DOI：
10.1128/mcb.24.8.3505-3513.2004
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发表时间：
2004-04-01
影响因子：
5.3
通讯作者：
Kadesch, T
中科院分区：
文献类型：
--
作者：
Ross, DA;Rao, PK;Kadesch, T
脂肪形成过程涉及一个复杂的基因表达程序，其中包括下调编码Hes-1的基因，Hes-1是Notch信号通路的靶标。为了确定Notch信号是否影响脂肪生成，我们将3T3-L1前脂肪细胞暴露于Notch配体Jagged1，发现分化显著减少。这种效应可以通过Hes-1的组成型表达来模拟。这种阻断与C/EBPalpha和PPARGamma诱导的完全丧失有关，并可以通过逆转录病毒表达C/EBPalpha或PPARGamma2来克服。令人惊讶的是，小干扰RNA(SiRNA)介导的3T3-L1细胞中Hes-1mRNA的下调也抑制了分化，这表明Hes-1在脂肪形成中发挥了额外的、必不可少的作用。这一作用可能与我们观察到的Notch信号和Hes-1下调编码DLK/Pref-1基因的转录有关，DLK/Pref-1是一种已知抑制3T3-L1细胞分化的蛋白质。这项研究的结果建立了Notch-Hes-1途径下游的一个新靶点，并表明Hes-1在脂肪细胞发育中具有双重作用。
The process of adipogenesis involves a complex program of gene expression that includes down-regulation of the gene encoding Hes-1, a target of the Notch signaling pathway. To determine if Notch signaling affects adipogenesis, we exposed 3T3-L1 preadipocytes to the Notch ligand Jagged1 and found that differentiation was significantly reduced. This effect could be mimicked by constitutive expression of Hes-1. The block was associated with a complete loss of C/EBPalpha and peroxisome proliferator-activated receptor gamma (PPARgamma) induction and could be overcome by retroviral expression of either C/EBPalpha or PPARgamma2. Surprisingly, small interfering RNA (siRNA)-mediated reduction of Hes-1 mRNA in 3T3-L1 cells also inhibited differentiation, suggesting an additional, obligatory role for Hes-1 in adipogenesis. This role may be related to our observation that both Notch signaling and Hes-1 down-regulate transcription of the gene encoding DLK/Pref-1, a protein known to inhibit differentiation of 3T3-L1 cells. The results presented in this study establish a new target downstream of the Notch-Hes-1 pathway and suggest a dual role for Hes-1 in adipocyte development.