Architectural changes of the extracellular matrix in compensatory lung growth (540.2)

Abstract

Compensatory growth of the remaining lung after murine pneumonectomy (PNX) involves the structural remodeling of the peripheral acini. Although the role of stem cells and local cellular proliferation is an area of active investigation, very little is known about the corresponding changes in the lung extracellular matrix (ECM). Post‐PNX adaptation of the elastin network, in particular, is essential for maintaining the mechanical and functional properties of the lung. Elastic fiber bundles concentrate particularly in the end bulbs of free septal alveolar edges shown in trans‐electron‐microscopic imaging and Verhoeff‐van‐Gieson staining. The elastic fibers form a continuous helical cable element, interconnecting alveolar entrance rings, spanning several levels of alveolar ducts. High‐resolution synchrotron radiation microscopy revealed this cord element running on the inside of alveolar ducts of infant murine lungs in the alveolar phase of lung development. The continuity of the elastic helix in adult c57bl/6 mice was visualized by scanning electron microscopy and by confocal microscopy of decellularized murine lung slices. Stereological estimates show an increased number of elastin‐containing septal edges during compensatory growth. The architectural changes in the murine ECM suggest active remodeling of the elastin network after PNX. The orientation of elastin in the septal tips of remodeling alveoli suggest the active participation of the elastin network in neoalveolarization. Consistent with these observations, the elastin cord element may be involved in the long‐range signaling essential for functional acinar remodeling.Grant Funding Source: NIH