title: Matrix metalloproteinase-2 from bronchial epithelial cells induces the proliferation of subepithelial fibroblasts.
abstract: BACKGROUND
  In bronchial asthma, subepithelial fibrosis in the conducting airways is associated with increased numbers of subepithelial fibroblasts.
  
  
  OBJECTIVE
  This study examined the hypothesis that MMP-2 from airway epithelial cells induces the proliferation of subepithelial fibroblasts.
  
  
  METHODS
  Using primary bronchial epithelial cells MMP-2, MT1-MMP and TIMP-2 mRNA expression were assessed by Northern blotting and RT-PCR. Primary bronchial epithelial cells transfected with constructs encoding pro-MMP-2 and MT1-MMP (MMP-14).
  
  
  RESULTS
  Transfected cells showed enhanced expression of the appropriate mRNA species by RT-PCR and enhanced MMP-2 or MT1-MMP activity by zymography. Active MMP-2 levels in epithelial supernatants were increased most by cotransfection with pro-MMP-2 and MT1-MMP encoding constructs. By measuring tritiated thymidine incorporation, supernatants from transfected cells were found to enhance DNA synthesis of primary airway fibroblast cultures compared with controls. There was a strong correlation (r = 0.9, P < 0.01) between MMP-2 levels in epithelial cell conditioned media and fibroblast proliferation as indicated by DNA synthesis. The MMP inhibitor 1,10-phenanthroline attenuated the increased proliferation, while the addition of exogenous purified MMP-2 alone also increased fibroblast proliferation.
  
  
  CONCLUSIONS
  Our results support a role for MMP-2 in mediating cross-talk between epithelial cells and myofibroblasts.
authors.affiliation: Respiratory Cell and Molecular Biology, Division of Infection, Inflammation and Repair, University of Southampton, Southampton General Hospital, Southampton, UK.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: R C
authors.initials: RC
authors.lastname: Benyon
authors.forename: S-H
authors.initials: SH
authors.lastname: Leir
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
authors.forename: P M
authors.initials: PM
authors.lastname: Lackie
mesh_terms: D001980:Bronchi / Q000201:enzymology*; D004847:Epithelial Cells / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
chemical_list: D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2