Upregulation of the 72-kDa type IV collagenase in epithelial and stromal cells during rat tracheal gland morphogenesis.

Submucosal glands secrete most of the mucus that lubricates the tracheal surface and protects it from irritants and infection. These glands develop postnatally in the rat, permitting convenient study of the mechanisms controlling this process. One such mechanism involves degradation of the supportive connective tissue matrix at the front of the growing glands. We recently showed that tracheal gland cell invasion of collagen gels in vitro is dependent on secretion of a 72-kDa type IV collagenase. In the present study, we show that the activity of this enzyme (also referred to as matrix metalloproteinase-2 or gelatinase A) is elevated at the time of gland development in vivo. That this increase is at least partly mediated at the level of steady-state mRNA was indicated by semiquantitative PCR analysis of gland-enriched, microdissected tissue samples. Immunohistochemistry revealed that the enzyme was present at the interface between the glands and extracellular matrix. In situ hybridization revealed that the cognate mRNA was present in epithelial cells of glands undergoing morphogenesis (particularly Postnatal Day 7) but not in those of adult glands or the surface epithelium. At all ages, stromal cells below the surface epithelium were labeled; labeling intensity was highest at the time and location of gland morphogenesis. These findings suggest that the 72-kDa type IV collagenase is developmentally regulated in gland and stromal cells at the level of steady-state mRNA and plays a role in the degradation of extracellular matrix during tracheobronchial gland morphogenesis.