The EGF-like protein Dlk1 inhibits notch signaling and potentiates adipogenesis of mesenchymal cells
The EGF-like protein Dlk1 inhibits notch signaling and potentiates adipogenesis of mesenchymal cells
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DOI：
10.1016/j.jmb.2006.10.043
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发表时间：
2007-04-13
影响因子：
5.6
通讯作者：
Laborda, Jorge
中科院分区：
文献类型：
--
作者：
Nueda, Maria-Luisa;Baladron, Victoriano;Laborda, Jorge
EGF样同源异型基因Dlk 1似乎作为脂肪形成的抑制剂起作用。过表达Dlk 1阻止3 T3-L1细胞的脂肪形成。Dlk 1缺陷小鼠肥胖;然而，脂肪组织仍然在Fc-dlk 1转基因小鼠中发育，表明Dlk 1不是脂肪形成的严格抑制剂。为了阐明Dlk 1在脂肪形成中的作用，我们研究了Dlk 1是否可以根据前体细胞的分化状态而在此过程中发挥不同的作用。我们发现Dlk 1是间充质C3 H10 T1/2细胞脂肪生成的增强剂。这种增强作用可以通过过表达整个蛋白质或细胞外含有EGF样的区域来触发，但不能通过过表达细胞内dlk 1序列来触发。此外，C3 H10 T1/2细胞与其他表达Dlk 1的细胞共培养，但不与缺乏Dlk 1表达的细胞共培养，增强了它们的成脂反应。Dlk 1对脂肪形成的增强作用与IGFI/胰岛素诱导后ERK 1/2活化的变化相关。最后，与其他细胞报道的一样，dlk 1在C3 H10 T1/2细胞中作为Notch信号传导抑制剂发挥作用，但Notch 1表达的抑制阻止了Dlk 1在脂肪形成中的增强作用。这些数据表明，Dlk 1可能会加强或抑制脂肪生成取决于细胞的情况下，和Notch 1的表达和激活是在这种情况下的重要因素。(c)2006爱思唯尔有限公司保留所有权利。
The EGF-like homeotic gene Dlk1 appears to function as an inhibitor of adipogenesis. Overexpression of Dlk1 prevents adipogenesis of 3T3-L1 cells. Dlk1-deficient mice are obese; however, adipose tissue still develops in Fc-dlk1 transgenic mice, suggesting that Dlk1 is not a strict inhibitor of adipogenesis. To clarify the role of Dlk1 in adipogenesis, we studied whether Dlk1 could act differently on this process depending upon the differentiation state of the precursor cells. We found that Dlk1 is a potentiator of adipogenesis for mesenchymal C3H10T1/2 cells. This potentiating effect can be triggered by overexpressing the entire protein or the extracellular EGF-like-containing region, but not by overexpressing the intracellular dlk1 sequence. In addition, coculture of C3H10T1/2 cells with other cells expressing Dlk1, but not with cells lacking Dlk1 expression, enhances their adipogenic response. Potentiation of adipogenesis by Dlk1 was associated with changes in the activation of ERK1/2 after IGFI/insulin induction. Finally, as reported with other cells, dlk1 functioned as a Notch signaling inhibitor in C3H10T1/2 cells, but inhibition of Notch1 expression prevented the potentiating effects of Dlk1 in adipogenesis. These data suggest that Dlk1 may potentiate or inhibit adipogenesis depending upon the cellular context, and that Notch1 expression and activation are important factors in this context. (c) 2006 Elsevier Ltd. All rights reserved.