Elastin in lung development

Abstract

Elastin is a critical component of the lung interstitium, providing the property of recoil to the vascular, conducting airway, and terminal airspace compartments of the lung. Elastic fibers, consisting of soluble tropoelastin monomers cross-linked on a preexisting scaffold of microfibrils, are produced primarily during late fetal and neonatal stages of development. The factors and molecular mechanisms regulating the cell type-specific and tightly temporally regulated expression of tropoelastin are currently under investigation. The onset and inductive phase of tropoelastin expression are characterized by increased transcription of the tropoelastin gene. Glucocorticoids accelerate this induction in fetal rats during the canalicular stage of lung development. Many additional factors regulate tropoelastin expression in cultured lung fibroblasts and vascular smooth muscle cells, but the in vivo roles of such mediators are still under investigation. Cell-cell interactions may also promote elastogenesis during lung development, as localization of tropoelastin mRNA in pseudo-glandular and canalicular lungs demonstrates a close spatial relationship between epithelium and adjacent elastogenic mesenchyme. Elastin metabolism is altered in several experimental models of bronchopulmonary dysplasia, characterized by abnormal lung morphological development, suggesting that normal elastin production and deposition is necessary for proper development of alveoli. Studies employing reverse genetics may prove useful in further defining the role of elastin in lung development.