TGF-β Down-regulates Apolipoprotein M Expression through the TAK-1-JNK-c-Jun Pathway in HepG2 Cells

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• 作者：Kun Ren ; Zhong-Cheng Mo ; Xing Liu ; Zhen-Li Tang ; Yue Jiang ; Xiao-Shan Peng…
• 关键词：ApoM ; TGF ; β ; TAK ; 1 ; JNK ; C ; Jun
• 刊名：Lipids
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：52
• 期：2
• 页码：109-117
• 全文大小：
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Lipidology; Neurochemistry; Medical Biochemistry; Nutrition; Medicinal Chemistry; Microbial Genetics and Genomics;
• 出版者：Springer Berlin Heidelberg
• ISSN：1558-9307
• 卷排序：52

文摘

Apolipoprotein M (apoM) is a relatively novel apolipoprotein that plays pivotal roles in many dyslipidemia-associated diseases; however, its regulatory mechanisms are poorly understood. Many cytokines have been identified that down-regulate apoM expression in HepG2 cells, among which transforming growth factor-β (TGF-β) exerts the most potent effects. In addition, c-Jun, a member of the activated protein 1 (AP-1) family whose activity is modulated by c-Jun N-terminal kinase (JNK), decreases apoM expression at the transcriptional level by binding to the regulatory element in the proximal apoM promoter. In this study, we investigated the molecular mechanisms through which TGF-β decreases the apoM level in HepG2 cells. The results revealed that TGF-β inhibited apoM expression at both the mRNA and protein levels in a dose- and time-dependent manner and that it suppressed apoM secretion. These effects were attenuated by treatment of cells with either SP600125 (JNK inhibitor) or c-Jun siRNA. 5Z-7-oxozeaenol [(a TGF-β-activated kinase 1 (TAK-1) inhibitor)] also attenuated the TGF-β-mediated inhibition of apoM expression and suppressed the activation of JNK and c-Jun. These results have demonstrated that TGF-β suppresses apoM expression through the TAK-1-JNK-c-Jun pathway in HepG2 cells.