Ontogeny of Rat Lung Type IV Collagenase mRNA Expression and Collagenolytic Activity during the Perinatal Period

Abstract

The extracellular matrix is important in the cellular differentiation and morphogenesis of the lung. The basement membrane (BM), an integral part of the extracellular matrix, is composed primarily of type IV collagen. The metabolism of type IV collagenase is important in remodeling of BM that occurs during growth. We examined the ontogeny of rat lung type IV collagenase mRNA expression, type IV collagenolytic activity and type IV collagen content during the perinatal period. In addition, the effect of prenatal glucocorticoid (GC) treatment on fetal lung type IV collagenase mRNA expression and type IV collagenolytic activity was studied. Lung polyadenylated RNA was extracted and subjected to Northern blot analysis and laser densitometry after hybridization with human type IV collagenase (∼72 kD) and rat actin cDNA probe. Type IV collagenolytic activity and type IV collagen concentration were quantitated by an enzymatic and a radioimmunoassay, respectively. While lung type IV collagenase mRNA to α-actin ratio and type IV collagenolytic activity were highest prior to birth (21-day fetus), the lung type IV collagen concentration was lowest at this time. Prenatal GC treatment did not influence type IV collagenase mRNA expression or the collagenolytic activity. A role for fetal lung type IV collagenase in preparation for the neonatal pulmonary vascular and/or alveolar adaption is proposed.

Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia

“…For obvious reasons, control samples could not be obtained from neonates weaned from the ventilator before day 3. Changes in MMP-2 level with time could, therefore, reflect either a decreased activity induced by injury, potentially interfering with lung development and/or repair, or a physiological transient increase activity induced by birth, as suggested by experiments in rats showing that lung type IV collagenase mRNA expression and type IV collagenolytic activity are highest before birth (23).…”

Effects of Antenatal Betamethasone on Maternal and Fetoplacental Matrix Metalloproteinases 2 and 9 Activities in Human Singleton Pregnancies

“…26 These processes are regulated by a balance between MMP-2 and its inhibitor, TIMP-2, which are highly expressed and activated during fetal lung development. [27][28][29] It has been suggested that activated MMP-2 in alveolar epithelial cells contributes to the formation of a large surface area. 5 Antenatal betamethasone is a potent lung-maturing agent.…”

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases during normal human pulmonary development

“…The site of MMP‐2 expression during fetal lung development differs in various animal models 11–13,17 , 20,21 , 27 . In the mouse fetus, MMP‐2 mRNA expression, using in situ zymography, was not detected in the epithelium but only in the mesenchymal cells from the early pseudoglandular stage onwards, 21 similar to our findings of MMP‐2 protein expression.…”

“…The findings of immunohistochemical and molecular biological studies using animal models indicate that some MMPs and TIMPs are involved in both lung morphogenesis and development 10–21 . MMP‐1, ‐8 and ‐13 have been shown to primarily degrade type I and III collagen, 6,7 which are the main components in the lung interstitium and the wall of intrapulmonary vessels in both the fetus and adult.…”