Postnatal lung development requires coordination of three processes-surface area expansion, microvascular growth, and matrix remodeling. Since normal elastin structure is important for lung morphogenesis, since physiological remodeling of lung elastin has never been defined, and since elastin remodeling is angiogenic, we sought to test the hypothesis that during lung development elastin is remodeled in a defined temporal-spatial pattern, that a novel protease is associated with this remodeling, and that angiogenesis is associated with elastin remodeling. By elastin in situ zymography, lung elastin remodeling increased 24-fold between embryonic day 15.5 (E15.5) and postnatal day 14 (PND14). Remodeling was restricted to major vessels and airways on PND1 with a 7-fold increase in alveolar wall elastin remodeling from PND1 to PND14. By inhibition assays and literature review, we identified chymotrypsin-like elastase 1 (CELA1) as a potential mediator of elastin remodeling. CELA1 mRNA levels increased 12-fold from E15.5 to PND9 and protein levels increased 3.4-fold from E18.5 to PND9. By co-staining experiments, the temporal-spatial pattern of CELA1 expression matched that of elastin remodeling and 58-85% of CELA1 (+) cells were <10 µm from an elastase signal. An association between elastin remodeling and angiogenesis was tested by similar methods. At PND7 and PND14, 60-95% of angiogenin (+) cells were associated with elastin remodeling. Both elastase inhibition and CELA1 silencing impaired angiogenesis in vitro. Our data defines the temporal-spatial pattern of elastin remodeling during lung development, demonstrates an association of this remodeling with CELA1, and supports role for elastin remodeling in regulating angiogenesis.
- Lung Development
- Pulmonary Vascular Development
- Matrix Remodeling
- Copyright © 2013, American Journal of Physiology - Lung Cellular and Molecular Physiology