The role of C/EBPδ in the early stages of adipogenesis
The role of C/EBPδ in the early stages of adipogenesis
复制标题
DOI：
10.1016/j.biochi.2009.02.002
复制
发表时间：
2009-05-01
期刊：
影响因子：
3.9
通讯作者：
Imagawa, Masayoshi
中科院分区：
文献类型：
--
作者：
Hishida, Tomoaki;Nishizuka, Makoto;Imagawa, Masayoshi
脂肪细胞分化是一个复杂的过程，由转录因子如过氧化体增殖物激活受体γ(PPARγ)和CCAAT/增强子结合蛋白(C/EBP)α触发和促进。关于分化过程中的级联反应，特别是早期阶段的事件，大部分仍有待阐明。在脂肪细胞分化的早期，C/EBPβ和C/EBP Delta基因被迅速诱导表达，然后激活PPARγ和C/EBPα的表达。C/EBPβ在有丝分裂克隆扩张(MCE)中也起着关键作用，MCE是前脂肪细胞在分化诱导剂刺激后不久发生的大约两轮有丝分裂，是脂肪细胞分化的必要步骤。然而，C/EBP家族的另一个成员C/EBP三角洲对MCE的影响尚不清楚。在本研究中，我们研究了C/EBP增量在脂肪形成的早期阶段中的作用。在分化开始后，C/EBP Delta基因的表达不是在增殖的前脂肪细胞中显著诱导，而是在生长停滞、可分化的细胞中被观察到。RNAi介导的C/EBP Delta基因敲除显著抑制了诱导分化后的细胞生长，并抑制了向高脂脂肪细胞的转化。此外，C/EBP Delta的沉默削弱了脂肪细胞分化因子(FAD)49的表达，该因子上调并在脂肪形成的早期发挥关键作用。综上所述，这些发现表明C/EBP Delta参与了脂肪细胞分化早期的MCE和基因表达。(C)2009年爱思唯尔·马森公司。版权所有。
Adipocyte differentiation is a complex process triggered and facilitated by transcription factors such as peroxisome proliferator-activated receptor gamma (PPAR gamma) and CCAAT/enhancer-binding protein (C/EBP) alpha. Most about the cascade underlying the differentiation process, especially events in the early stages, remain to be elucidated. Early on in adipocyte differentiation, the C/EBP beta and C/EBP delta genes are rapidly induced to express and later activate PPAR gamma and C/EBP alpha expression. C/EBP beta also plays a crucial role in mitotic clonal expansion (MCE), the approximately two rounds of mitosis which occurs soon after pre-adipocytes are stimulated by differentiation inducers and a necessary step for adipocyte differentiation. However, the effect of C/EBP delta, another member of the C/EBP family, on MCE remains unclear. In the present study, we investigated the role of C/EBP delta in the early stages of adipogenesis. A remarkable induction of C/EBP delta gene expression after the initiation of differentiation was observed not in proliferating preadipocytes, but in growth-arrested, differentiable cells. RNAi-mediated knockdown of C/EBP delta dramatically suppressed cell growth after differentiation was induced, and inhibited conversion into lipid-laden adipocytes. Furthermore, silencing of C/EBP delta impaired the expression of factor for adipocyte differentiation (fad) 49, which is up-regulated and plays a crucial role early in adipogenesis. Taken together, these findings show that C/EBP delta is involved in MCE and gene expression in the early stages of adipocyte differentiation. (C) 2009 Elsevier Masson SAS. All rights reserved.