E4BP4 mediates glucocorticoid-regulated adipogenesis through COX2. (15th July 2017)

• Record Type: Journal Article
• Authors: Yang, Yang; Wei, Hongkui; Song, Tongxing; Cai, Anle; Zhou, Yuanfei; Peng, Jie; Jiang, Siwen; Peng, Jian
• Is Part Of: Molecular and cellular endocrinology. Volume 450(2017)
• Page Start: 43
• Page End: 53
• Publication Date: 2017-07-15
• Subjects: E4BP4 -- Adipogenesis -- 3T3-L1 -- Dexamethasone -- GR -- COX2; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2017.04.015
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: 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 overexpression 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. Highlights: E4BP4 acts as a key pro-adipogenic transcription factor in adipocyte differentiation. Glucocorticoid (dexamethasone) induces E4BP4 expression via GR and CREB in adipogenesis. E4BP4 mediates the actions of glucocorticoid in adipocyte differentiation. E4BP4 promotes adipogenesis through transcriptionally represseing COX2.