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 t hem from the underlying connective tissue. At late fetal gestation, th is basement membrane is occasionally disrupted, allowing epithelial cy toplasmic extensions to reach in close proximity of the interstitial f ibroblast. The cellular source and enzymes responsible for the focal d egradation 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 enric hed in the expression of 72-kDa type IV collagenase mRNA. Zymography s howed that both cell types actively secrete 72- and 92-kDa type IV col lagenases. Conditioned medium of fibroblasts contained more gelatin de grading activity than that of epithelial cells. At the time of appeara nce of basement membrane discontinuities (19-21 days, term = 22 days), 72-kDa type IV collagenase mRNA expression in fibroblasts increased w hile that of epithelial cells remained constant. Gelatinolytic activit y of fibroblast conditioned medium also increased during this period. In contrast, type IV collagen gene expression decreased in both epithe lial cells and fibroblasts. These data are compatible with a role for type IV collagenases in the genesis of basement membrane disruptions d uring late fetal lung development. (C) 1995 Academic Press, Inc.