title: Adiponectin upregulates prolyl-4-hydroxylase α1 expression in interleukin 6-stimulated human aortic smooth muscle cells by regulating ERK 1/2 and Sp1.
abstract: Adiponectin is an anti-atherogenic adipokine that inhibits the development of plaque by mechanisms that are not completely understood. Extracellular matrix (ECM) may have a role in the pathogenesis of atherosclerosis. We explored the effect and mechanisms of adiponectin on the synthesis of prolyl-4-hydroxylase (P4H) in interleukin 6 (IL-6)-stimulated human aortic smooth muscle cells (HASMCs). P4Hα1 mRNA level was quantified by RT-PCR, the protein levels of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and P4Hα1 were quantified by western blot analysis, and activation of specific protein 1 (Sp1) was determined by electrophoretic mobility shift assay and subcellular localization of Sp1 by immunofluorescence analysis. Adiponectin significantly increased P4Hα1 mRNA and protein levels in IL-6-stimulated HASMCs in a dose- and time-dependent manner. As well, ERK1/2 and Sp1 played a crucial role in the effect of adiponectin upregulating P4Hα1 expression in IL-6-stimulated HASMCs. Adiponectin abrogated the effects of IL-6 on collagen III level, which may indicate that P4Hα1 is essential for folding the procollagen polypeptide chains into stabilized collagen. Adiponectin attenuates IL-6-inhibited P4Hα1 synthesis and stabilizes collagen formation in HASMCs through a Sp1-ERK1/2-P4Hα1-dependent pathway.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Cai
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011393:Procollagen-Proline Dioxygenase / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D015850:Interleukin-6; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; C510863:P4HA1 protein, human; D011393:Procollagen-Proline Dioxygenase; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3