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

Xu, J., Benyon, R.C., Leir, S.H., Zhang, S., Holgate, S.T. and Lackie, P.M. (2002) Matrix metalloproteinase-2 from bronchial epithelial cells induces the proliferation of subepithelial fibroblasts. Clinical & Experimental Allergy, 32 (6), 881-888. (doi:10.1046/j.1365-2745.2002.01386.x).

Abstract

BackgroundIn bronchial asthma, subepithelial fibrosis in the conducting airways is associated with increased numbers of subepithelial fibroblasts.
ObjectiveThis study examined the hypothesis that MMP-2 from airway epithelial cells induces the proliferation of subepithelial fibroblasts.
MethodsUsing 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).
ResultsTransfected 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.
ConclusionsOur results support a role for MMP-2 in mediating cross-talk between epithelial cells and myofibroblasts.

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Contributors

Author: P.M. Lackie

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