title: Synergistic induction of monocyte chemoattractant protein-1 by integrins and platelet-derived growth factor via focal adhesion kinase in mesangial cells.
abstract: BACKGROUND
  Growth factors, extracellular matrix and its receptor integrins are upregulated in various glomerular diseases. We investigated the mechanism of collaboration between integrins and platelet-derived growth factor (PDGF) in focal adhesion kinase (FAK)- and extracellular signal-related kinase (ERK)1/2-mediated signal pathways that lead to monocyte chemoattractant protein (MCP)-1 expression in cultured rat mesangial cells (MCs).
  
  
  METHODS
  Serum-starved MCs were plated on fibronectin- or polylysine-coated plates with or without PDGF, and examined for phosphorylation of ERK1/2, mitogen-activated protein or ERK kinase (MEK)1/2 and FAK by western blotting, and for expression of MCP-1 mRNA and protein by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The effects of dominant-negative FAK on MCP-1 expression were examined.
  
  
  RESULTS
  Cell adhesion to fibronectin increased phosphorylation of FAK, MEK1/2 and ERK1/2, and induced MCP-1 mRNA and protein expression. PDGF increased phosphorylation of FAK, MEK1/2 and ERK1/2 even without cell adhesion to fibronectin, and induced MCP-1 mRNA and protein expression. PDGF with integrin activation by fibronectin synergistically increased phosphorylation of FAK, MEK1/2 and ERK1/2, and expression of MCP-1 mRNA and protein. Dominant-negative FAK attenuated fibronectin enhancement of PDGF-induced ERK1/2 phosphorylation and MCP-1 expression, indicating involvement of FAK in this signalling.
  
  
  CONCLUSIONS
  Our results suggest the cooperative role of integrin and PDGF receptor in activation of the ERK pathway possibly via FAK in MCs. The synergistic activation of integrin and PDGF signalling may play an important role in the progression of glomerular diseases through the induction of MCP-1.
authors: Kidney Center, University of Occupational and Environmental Health University Hospital, 1-1 Iseigaoka, Yahatanishi, Kitakyushu 807-8555, Japan.
authors: Kaori
authors: K
authors: Kanegae
authors: Masahito
authors: M
authors: Tamura
authors: Narutoshi
authors: N
authors: Kabashima
authors: Ryota
authors: R
authors: Serino
authors: Masaki
authors: M
authors: Tokunaga
authors: Shigeru
authors: S
authors: Oikawa
authors: Yasuhide
authors: Y
authors: Nakashima
mesh_terms: D000818:Animals; D001483:Base Sequence; D000077214:Becaplermin; D002448:Cell Adhesion; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D004247:DNA / Q000235:genetics; D004357:Drug Synergism; D005353:Fibronectins / Q000008:administration & dosage* / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage* / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D015398:Signal Transduction
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D005353:Fibronectins; D016023:Integrins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D004247:DNA