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Chapter 17 - The Lung Structure Maintenance Program: Sustaining Lung Structure during Adulthood and Implications for COPD Risk

Published online by Cambridge University Press:  05 April 2016

By
Norbert F. Voelkel  and
Masahiro Sakagami
Edited by
Alan H. Jobe ,
Jeffrey A. Whitsett  and
Steven H. Abman
Alan H. Jobe
Affiliation:
University of Cincinnati
Jeffrey A. Whitsett
Affiliation:
Cincinnati Children’s Hospital
Steven H. Abman
Affiliation:
University of Colorado School of Medicine
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Summary

Abstract

During lung development, alveolarization and the formation of the vast capillary network require the coordinate interactions of several growth factors during different stages of lung organ building; prominent among those are FGF10, PDGF, and epithelially secreted VEGF. Effective VEGF signaling is also required for the structure maintenance of the adult lung, as genetic modifications in mice and VEGF receptor blockade in adult rats lead to emphysematous airspace enlargement. The remarkable dependence of lung microvascular endothelial cells for their survival on autocrine VEGF signaling is illustrated in the lungs from patients with endstage COPD/emphysema; examination of such lungs shows severely decreased expression of VEGF and of VEGF receptor 1 and 2 proteins and of the VEGF gene upstream transcription factor HIF1 alpha. Copper is required for angiogenesis, and copper depletion causes emphysema in rodents. Thus copper is participating in the maintenance of the adult lung structure also because of its requirement for the activity of the collagen-crosslinking enzyme lysyl oxidase and the oxidant defense enzyme CuZn SOD. In addition, the “sphingosine-1-phosphate/ceramide rheostat” plays a role in the homeostasis of the lung structure. Taken together, this chapter provides the background and the rationale for concepts that can explain how genetic defects and environmental challenges can jeopardize the homeostatic lung structure maintenance program and cause destructive lung diseases in the adult.

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Type
Chapter
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Fetal and Neonatal Lung Development
Clinical Correlates and Technologies for the Future
 , pp. 303 - 310
Publisher: Cambridge University Press
Print publication year: 2016

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