Matrix metalloproteinase-2 from bronchial epithelial cells induces the proliferation of subepithelial fibroblasts

J. Xu, R. C. Benyon, S. H. Leir, S. Zhang, S. T. Holgate, P. M. Lackie*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)881-888
Number of pages8
JournalClinical and Experimental Allergy
Issue number6
StatePublished - 2002


  • Airway
  • Fibrosis
  • MMP-14
  • MMP-2
  • MT1-MMP
  • Myofibroblast
  • TIMP-2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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