title: TGF-β Down-regulates Apolipoprotein M Expression through the TAK-1-JNK-c-Jun Pathway in HepG2 Cells.
abstract: 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.
authors.affiliation: Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Ren
authors.affiliation: Department of Histology and Embryology, University of South China, Hengyang, 421001, Hunan, China.
authors.forename: Zhong-Cheng
authors.initials: ZC
authors.lastname: Mo
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, China.
authors.forename: Zhen-Li
authors.initials: ZL
authors.lastname: Tang
authors.affiliation: Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, China.
authors.forename: Xiao-Shan
authors.initials: XS
authors.lastname: Peng
authors.affiliation: Clinical Research Institution, The First Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China.
authors.forename: Qing-Hai
authors.initials: QH
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, China.|Department of Histology and Embryology, University of South China, Hengyang, 421001, Hunan, China.
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Shi
authors.affiliation: Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, China. ghyi6108@163.com.
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Yi
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D001053:Apolipoproteins / Q000235:genetics* / Q000378:metabolism*; D000075243:Apolipoproteins M; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D054834:Lipocalins / Q000235:genetics* / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012118:Resorcinols / Q000494:pharmacology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D000099151:MAP Kinase Kinase Kinase 7; D015025:Zearalenone / Q000008:administration & dosage
chemical_list: D000873:Anthracenes; D001053:Apolipoproteins; D000075243:Apolipoproteins M; D007783:Lactones; D054834:Lipocalins; D020930:MAP Kinase Kinase Kinases; D016755:Proto-Oncogene Proteins c-jun; D012118:Resorcinols; D016212:Transforming Growth Factor beta; D000099151:MAP Kinase Kinase Kinase 7; C505734:7-oxozeanol; D015025:Zearalenone; C400523:APOM protein, human; C432165:pyrazolanthrone
keywords: ApoM; C-Jun; JNK; TAK-1; TGF-β