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.

Expression Profiles of the Mouse Lung Identify a Molecular Signature of Time-to-Birth

“…The gene that contributed the second most to PC2 in L1 was Eln, the gene encoding the major component of elastic fibers. Elastic fibers are responsible for providing tissue elastic recoil essential for expiration and has previously been shown to be essential for survival at birth (25,26). However, the complex expression pattern for elastin (Eln) expression during lung development (15) is not correlated with the time-to-birth and thus would not clearly indicate its necessity for the transition to air breathing.…”

Lysyl Oxidase Activity Is Dysregulated during Impaired Alveolarization of Mouse and Human Lungs

“…The production and remodeling of the ECM are critical processes required for the secondary septation of the developing lung and the production and maturation of functional pulmonary gas exchange units (37,38). The pathogenic mechanisms that result in the perturbed deposition and remodeling of the ECM observed in important developmental lung diseases such as BPD (12,15) are poorly understood.…”

Highly conserved transcriptional responses to mechanical ventilation of the lung

“…ELN, which provides important structural properties to the lung, is upregulated by mechanical ventilation in premature neonatal lambs (59), baboons (56,59), and mice (11). ELN is normally expressed in the lung during development and is quiescent in healthy adult lung (52), but aberrant ELN expression is induced in fibrotic disorders of the lung (72), in pulmonary hypertension (78), and during lung growth in response to pneumonectomy (47). GPC3, which has not been previously associated with VILI, was repressed in our samples and is repressed by TGF-␤ (66).…”