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TGF‐β Down‐regulates Apolipoprotein M Expression through the TAK‐1‐JNK‐c‐Jun Pathway in HepG2 Cells
Author(s) -
Ren Kun,
Mo ZhongCheng,
Liu Xing,
Tang ZhenLi,
Jiang Yue,
Peng XiaoShan,
Zhang QingHai,
Shi JinFeng,
Yi GuangHui
Publication year - 2017
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-016-4227-9
Subject(s) - c jun , apolipoprotein b , kinase , clinical chemistry , chemistry , transforming growth factor , signal transduction , microbiology and biotechnology , transcription factor , biology , biochemistry , gene , cholesterol
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.