DEGRADATION OF TYPE-IV COLLAGEN DURING THE DEVELOPMENT OF FETAL-RAT LUNG

Lung structure undergoes rapid remodeling during late gestation as a f unctional respiratory unit is formed. To determine the role of collage n turnover in this process, particularly the basement membrane compone nt, we studied the degradation of collagen in a series of fetal rats f rom day 18 of gestation to full term. During the period of rapid cell proliferation to day 20, the collagen level per milligram of lung did not change though the mte of synthesis increased. More than 40% of new collagen was rapidly degraded. At the end of the growth phase, collag en synthesis rose rapidly as the total collagen content increased in t he lung. Over this period, little Type I collagenase activity could be detected, but degradation of Type IV collagen was readily measured an d was maximal at 18 to 20 days. The enzyme(s) was almost all present i n the active form, and evidence for dissolution of the subepithelial b asement membrane was also found by electron microscopy. Using isolated fetal epithelial cells and fibroblasts, supernatants of both cell typ es showed degradative activity for Type IV collagen, particularly at d ays 18 to 20. The major enzyme involved appears to be a 72 kD collagen ase, as shown by zymography and by mRNA expression in both cell types. The results demonstrate that rapid degradation of Type IV collagen oc curs during the growth phase of late fetal lung development, and that both epithelial and stromal cells contribute to collagenolytic activit y.