PMID- 21829524 OWN - NLM STAT- MEDLINE DCOM- 20111206 LR - 20211020 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 6 IP - 7 DP - 2011 TI - Adiponectin upregulates prolyl-4-hydroxylase alpha1 expression in interleukin 6-stimulated human aortic smooth muscle cells by regulating ERK 1/2 and Sp1. PG - e22819 LID - 10.1371/journal.pone.0022819 [doi] LID - e22819 AB - 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). P4Halpha1 mRNA level was quantified by RT-PCR, the protein levels of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and P4Halpha1 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 P4Halpha1 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 P4Halpha1 expression in IL-6-stimulated HASMCs. Adiponectin abrogated the effects of IL-6 on collagen III level, which may indicate that P4Halpha1 is essential for folding the procollagen polypeptide chains into stabilized collagen. Adiponectin attenuates IL-6-inhibited P4Halpha1 synthesis and stabilizes collagen formation in HASMCs through a Sp1-ERK1/2-P4Halpha1-dependent pathway. FAU - Li, Li AU - Li L AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Shandong University Qilu Hospital, Jinan, Shandong, China. FAU - Zhang, Ke AU - Zhang K FAU - Cai, Xiao-Jun AU - Cai XJ FAU - Feng, Min AU - Feng M FAU - Zhang, Yun AU - Zhang Y FAU - Zhang, Mei AU - Zhang M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110729 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Adiponectin) RN - 0 (Interleukin-6) RN - 0 (RNA, Messenger) RN - 0 (Sp1 Transcription Factor) RN - EC 1.14.11.2 (P4HA1 protein, human) RN - EC 1.14.11.2 (Procollagen-Proline Dioxygenase) RN - EC 2.7.11.24 (MAPK1 protein, human) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) SB - IM MH - Adiponectin/*pharmacology MH - Aorta/cytology/drug effects/*metabolism MH - Blotting, Western MH - Cells, Cultured MH - Electrophoretic Mobility Shift Assay MH - Enzyme-Linked Immunosorbent Assay MH - Gene Expression Regulation MH - Humans MH - Interleukin-6/*pharmacology MH - Mitogen-Activated Protein Kinase 1/genetics/*metabolism MH - Mitogen-Activated Protein Kinase 3/genetics/*metabolism MH - Muscle, Smooth, Vascular/cytology/drug effects/*metabolism MH - Phosphorylation MH - Procollagen-Proline Dioxygenase/genetics/*metabolism MH - RNA, Messenger/genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction MH - Sp1 Transcription Factor/genetics/*metabolism PMC - PMC3146504 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2011/08/11 06:00 MHDA- 2011/12/13 00:00 PMCR- 2011/07/29 CRDT- 2011/08/11 06:00 PHST- 2011/04/14 00:00 [received] PHST- 2011/06/29 00:00 [accepted] PHST- 2011/08/11 06:00 [entrez] PHST- 2011/08/11 06:00 [pubmed] PHST- 2011/12/13 00:00 [medline] PHST- 2011/07/29 00:00 [pmc-release] AID - PONE-D-11-06807 [pii] AID - 10.1371/journal.pone.0022819 [doi] PST - ppublish SO - PLoS One. 2011;6(7):e22819. doi: 10.1371/journal.pone.0022819. Epub 2011 Jul 29.