title: MCP-1 stimulates MMP-9 expression via ERK 1/2 and p38 MAPK signaling pathways in human aortic smooth muscle cells.
abstract: OBJECTIVE
  We investigated the molecular mechanism underlying the role of monocyte chemoattractant protein-1 (MCP-1) in the formation and development of human abdominal aortic aneurysm (AAA).
  
  
  METHODS
  We examined protein expression profiles using a protein array and found that MCP-1 was the most highly expressed protein in AAA tissues compared with normal aortas. To investigate the potential mechanism of MCP-1 involvement in the pathogenesis of AAA, we treated human aortic smooth muscle cells (HASMCs) with human recombinant MCP-1.
  
  
  RESULTS
  MCP-1 was the most highly expressed protein in AAA tissues compared with normal aorta; matrix metalloproteinase-9 (MMP-9) expression was also significantly increased. Treatment with MCP-1 significantly increased the expression and activation of MMP-9 and activated the three major mitogen activated protein kinases (MAPKs) extracellular signal regulated kinase (ERK), c-Jun amino terminal kinase (JNK1/2) and p38 MAPK. Furthermore, MCP-1-induced secretion of MMP-9 was inhibited by U0126 (inhibitor of the ERK 1/2 pathway) and SB203580 (inhibitor of the p38 MAPK pathway), but not SP600125 (inhibitor of the JNK1/2 pathway).
  
  
  CONCLUSIONS
  These data demonstrate that MCP-1 stimulates secretion of MMP-9 directly through the ERK1/2 and p38 MAPK mediated pathways in HASMCs. Thus, inhibition of this molecular mechanism might be a potential therapeutic target in the non-surgical treatment of AAA.
authors.affiliation: Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Ci-Qiu
authors.initials: CQ
authors.lastname: Yang
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Song-Qi
authors.initials: SQ
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Li
authors.forename: Shu-Xin
authors.initials: SX
authors.lastname: Kong
authors.forename: Rui-Ming
authors.initials: RM
authors.lastname: Liu
authors.forename: Shen-Ming
authors.initials: SM
authors.lastname: Wang
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Lv
mesh_terms: D001011:Aorta / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D001483:Base Sequence; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000502:physiology*; D017931:DNA Primers; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D018932:Chemokine CCL2; D017931:DNA Primers; D048051:p38 Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9