Expression and characterization of type IV collagenases in rat lung cells during development

Fetal type II epithelial cells rest on a basal lamina which separate them from the underlying connective tissue. At late fetal gestation, this basement membrane is occasionally disrupted, allowing epithelial cytoplasmic extensions to reach in close proximity of the interstitial fibroblast. The cellular source and enzymes responsible for the focal degradation of the basal membrane remains to be defined. In the present study, we examined the developmental expression of basement membrane associated type IV collagen and its degrading enzymes. Both fetal lung epithelial cells and fibroblasts expressed 72-kDa type IV collagenase and type IV (alpha 1) (alpha 2) collagen genes. Fibroblasts were enriched in the expression of 72-kDa type IV collagenase mRNA. Zymography showed that both cell types actively secrete 72- and 92-kDa type IV collagenases. Conditioned medium of fibroblasts contained more gelatin degrading activity than that of epithelial cells. At the time of appearance of basement membrane discontinuities (19-21 days, term = 22 days), 72-kDa type IV collagenase mRNA expression in fibroblasts increased while that of epithelial cells remained constant. Gelatinolytic activity of fibroblast conditioned medium also increased during this period. In contrast, type IV collagen gene expression decreased in both epithelial cells and fibroblasts. These data are compatible with a role for type IV collagenases in the genesis of basement membrane disruptions during late fetal lung development.