Notch-1 controls the expression of fatty acid-activated transcription factors and is required for adipogenesis
Notch-1 controls the expression of fatty acid-activated transcription factors and is required for adipogenesis
复制标题
DOI：
10.1074/jbc.272.47.29729
复制
发表时间：
1997-11-21
影响因子：
4.8
通讯作者：
Laborda, J
中科院分区：
文献类型：
--
作者：
Garces, C;RuizHidalgo, MJ;Laborda, J
Notch是同质性表皮生长因子样蛋白家族的一种跨膜受体，参与细胞间信号传导以控制细胞发育过程中的命运。在体外实验中，缺乏细胞外区域的激活Notch-1构建物阻止了几种哺乳动物细胞的分化，然而，这种作用绕过了Notch-1参与的正常细胞间相互作用机制。在激素诱导的3T3-L1成纤维细胞的脂肪细胞分化中，这是一种需要细胞间接触的脂肪形成的典型模型，与其他分化模型不同，Notch-1的表达和功能是脂肪形成的必要条件，通过反义Notch-1构建的Notch-1表达受损会阻止脂肪细胞分化。旨在阻断Notch/配体相互作用的策略也阻断了脂肪的形成，暗示Notch是细胞间信号传导的关键分子，这是分化所必需的。抑制Notch-1的表达或功能会降低过氧化物酶体增殖体激活受体的表达，这些转录因子控制脂肪细胞分化，并在细胞融合时上调。这些结果暗示Notch通过控制该过程的主要调节因子的表达而参与3T3-L1细胞进行脂肪形成。
Notch, a transmembrane receptor member of the homeotic epidermal growth factor-like family of proteins, participates in cell-to-cell signaling to control cell fate during development, Activated Notch-1 constructs lacking the extracellular region prevent differentiation of several mammalian cells in vitro, This effect, however, bypasses the normal mechanisms of cell-to-cell interactions in which Notch-1 participates, We investigated the role of Notch-1. in the hormone-induced adipocyte differentiation of 3T3-L1 fibroblasts, a paradigmatic model of adipogenesis that requires cell-to-cell contact, Unlike other differentiation models, Notch-1 expression and function were necessary conditions for adipogenesis, Impaired Notch-1 expression by antisense Notch-1 constructs prevented adipocyte differentiation. Strategies aimed at blocking putative Notch/ligand interactions also blocked adipogenesis, implicating Notch as a critical molecule in cell-to-cell signaling necessary for differentiation, Inhibition of Notch-1 expression or function decreased the expression of peroxisomal proliferator-activated receptors delta and gamma, transcription factors that control adipocyte differentiation and that are up-regulated at cell confluence, These results implicate Notch in the commitment of 3T3-L1 cells to undergo adipogenesis by controlling the expression of the principal regulators of this process.