Degradation of Type IV Collagen during the Development of Fetal Rat Lung

Abstract

Lung structure undergoes rapid remodeling during late gestation as a functional respiratory unit is formed. To determine the role of collagen turnover in this process, particularly the basement membrane component, we studied the degradation of collagen in a series of fetal rats from 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 rate of synthesis increased. More than 40% of new collagen was rapidly degraded. At the end of the growth phase, collagen synthesis rose rapidly as the total collagen content increased in the lung. Over this period, little Type I collagenase activity could be detected, but degradation of Type IV collagen was readily measured and was maximal at 18 to 20 days. The enzyme(s) was almost all present in the active form, and evidence for dissolution of the subepithelial basement membrane was also found by electron microscopy. Using isolated fetal epithelial cells and fibroblasts, supernatants of both cell types showed degradative activity for Type IV collagen, particularly at days 18 to 20. The major enzyme involved appears to be a 72 kD collagenase, as shown by zymography and by mRNA expression in both cell types. The results demonstrate that rapid degradation of Type IV collagen occurs during the growth phase of late fetal lung development, and that both epithelial and stromal cells contribute to collagenolytic activity.