title: Overexpression of receptor for advanced glycation end products induces monocyte chemoattractant protein-1 expression in rat vascular smooth muscle cell line.
abstract: OBJECTIVE
  The receptor for advanced glycation end-products (RAGE) has been suggested to play a pivotal role in the development of diabetic vasculopathy and atherosclerosis; however, due to its low expression, the physiological role of RAGE in vascular smooth muscle cells (VSMC) remains unknown.
  
  
  METHODS
  Using VSMC lines stably expressing RAGE (RAGE-A10), we studied the molecular mechanism by which S100B, a RAGE ligand, induces proinflammatory gene expression.
  
  
  RESULTS
  S100B induced NF-κB activation and the expression of several proinflammatory genes (MCP-1, IL-6, ICAM-1) at mRNA and protein levels in RAGE-A10, among which MCP-1 expression was the most robust. S100B-induced MCP-1 expression was dose-dependently blocked by inhibitors of JNK (SP600125), p38 (SB203580), MEK-1 (U0126) as well as NF-κB (Bay117085). In RAGE-A10, S100B activated JNK, MEK-1 and p38. S100B-induced MCP-1 promoter activity via NF-κB binding sites and nuclear translocation of NF-κB p65 subunit were blocked by SP600125, U0126, and SB203580 in RAGE-A10.
  
  
  CONCLUSIONS
  Our study demonstrates that S100B increased MCP-1 expression via NF-κB and mitogen-activated protein kinase (JNK, ERK1/2, and p38) pathways in RAGE-overexpressed A10 cell lines. Thus, RAGE-A10 could be a useful cell model for studying the molecular mechanism(s) of up-regulated RAGE in the vasculature.
authors.affiliation: Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Bunkyo-ku, Tokyo, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Hayakawa
authors.forename: Takanobu
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Naoko
authors.initials: N
authors.lastname: Sekizawa
authors.forename: Toru
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hirata
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins; D018799:Intercellular Adhesion Molecule-1; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases