Differential Expression of Angiogenic Gene Networks during Post-natal Lung Alveolarization

Abstract

Prematurity of birth is the leading cause of death in children under 5 years of age. Preterm birth rates are steadily increasing across the globe due to advancements in medical knowledge and procedures that allow progressively earlier fetuses to survive outside of the mother’s womb. Bronchopulmonary dysplasia is a chronic lung disorder that can result from mechanical ventilation and long-term oxygen use in preterm neonates. This condition is characterized by disrupted pulmonary alveolar septation, alveolar hypoplasia, and fewer, larger alveoli that lead to decreased surface area available for gas exchange. Despite notable advances in preterm care, bronchopulmonary dysplasia results in a large number of short- and long-term morbidities, thus more advanced treatments that facilitate lung development in this subset of pediatric patients are sorely needed. In this study, we examined alterations in the gene expression profiles of 81 genes involved in angiogenesis during the process of normal alveolarization in mouse lungs. Our data revealed that alveolarization can be largely divided into early (1 week postnatal) and late (4 to 8 weeks postnatal) stages based on angiogenic gene expression profiles. In summary, our findings provide molecularlevel data illustrating the dynamic alterations in pulmonary angiogenesis during postnatal alveolarization. This knowledge can be used to provide a better understanding of normal lung development, and set the stage for discovering targeted therapies that can assist in pulmonary functioning for preterm infants.