E4BP4 mediates glucocorticoid-regulated adipogenesis through COX2
E4BP4 mediates glucocorticoid-regulated adipogenesis through COX2
复制标题
E4BP4 通过 COX2 介导糖皮质激素调节的脂肪生成
DOI：
10.1016/j.mce.2017.04.015
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发表时间：
2017-07-15
影响因子：
4.1
通讯作者：
Peng, Jian
中科院分区：
文献类型：
--
作者：
Yang, Yang;Wei, Hongkui;Peng, Jian
脂肪生成是由糖皮质激素通过对糖皮质激素受体（GR）靶基因的转录调控来介导的。然而，GR参与脂肪生成的机制迄今仍未得到充分阐释。在本研究中，发现E4启动子结合蛋白4（E4BP4）在前脂肪细胞的脂肪分化中起着关键作用。功能获得和功能缺失研究表明，E4BP4在3T3 - L1细胞中作为脂肪生成的正向调节因子。在脂肪生成过程中，糖皮质激素（地塞米松）通过GR和环磷腺苷效应元件结合蛋白（CREB）显著诱导E4BP4的表达。敲低E4BP4可消除地塞米松诱导的脂肪生成，而E4BP4的过表达则部分解释了地塞米松在脂肪分化中的作用。启动子缺失分析证实，E4BP4在转录水平上抑制COX2启动子活性，而COX2的过表达则逆转了E4BP4对脂肪生成的促进作用。因此，在糖皮质激素相关的脂肪细胞分化过程中，E4BP4通过反式抑制COX2，充当关键的促脂肪生成转录因子。（C）2017爱思唯尔出版社。保留所有权利。
Adipogenesis is mediated by glucocorticoids via transcriptional regulation of glucocorticoid receptor (GR) target genes. However, the mechanism by which GR participates in adipogenesis has hitherto been poorly characterized. In this study, E4 promoter-binding protein 4 (E4BP4) was found to have a critical role in adipogenic differentiation of preadipocytes. Gain-of-function and loss-of-function studies revealed that E4BP4 acts as a positive regulator of adipogenesis in 3T3-L1 cells. E4BP4 was markedly induced by glucocorticoid (dexamethasone) via GR and cAMP response element-binding protein (CREB) during adipogenesis. Knockdown of E4BP4 abolished dexamethasone-induced adipogenesis, and over expression of E4BP4 partially accounted for the actions of dexamethasone in adipogenic differentiation. Promoter deletion analysis confirmed that E4BP4 transcriptionally represses COX2 promoter activity, whereas COX2 overexpression reversed the acceleration of E4BP4 in adipogenesis. Thus, E4BP4 acts as a key pro-adipogenic transcription factor by trans-repressing COX2 in glucocorticoid-associated adipocyte differentiation. (C) 2017 Elsevier B.V. All rights reserved.