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

Summary 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