Control mechanisms of lung alveolar development and their disorders in bronchopulmonary dysplasia.
Bronchopulmonary dysplasia (BPD) is a chronic lung disease that occurs in very premature infants and is characterized by impaired alveologenesis. This ultimate phase of lung development is mostly postnatal and allows growth of gas-exchange surface area to meet the needs of the organism. Alveologenesis is a highly integrated process that implies cooperative interactions between interstitial, epithelial, and vascular compartments of the lung. Understanding of its underlying mechanisms has considerably progressed recently with identification of structural, signaling, or remodeling molecules that are crucial in the process. Thus, the pivotal role of elastin deposition in lung walls has been demonstrated, and many key control-molecules have been identified, including various transcription factors, growth factors such as platelet-derived growth factor, fibroblast growth factors, and vascular endothelial growth factor, matrix-remodeling enzymes, and retinoids. BPD-associated changes in lung expression/content have been evidenced for most of these molecules, especially for signaling pathways, through both clinical investigations in premature infants and the use of animal models, including the premature baboon or lamb, neonatal exposure to hyperoxia in rodents, and maternal-fetal infection. These findings open therapeutic perspectives to correct imbalanced signaling. Unraveling the intimate molecular mechanisms of alveolar building appears as a prerequisite to define new strategies for the prevention and care of BPD.
Bourbon
Jacques
J
Inserm U651-Université Paris XII, Faculté de Médecine, Créteil, France. Jacques.Bourbon@creteil.inserm.fr
Boucherat
Olivier
O
Chailley-Heu
Bernadette
B
Delacourt
Christophe
C
D000818:Animals; D001997:Bronchopulmonary Dysplasia / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D004549:Elastin / Q000096:biosynthesis / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006801:Humans; D000860:Hypoxia; D007231:Infant, Newborn; D008168:Lung / Q000378:metabolism; D008954:Models, Biological; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D047928:Premature Birth; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011659:Pulmonary Gas Exchange; D012176:Retinoids / Q000378:metabolism; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D010982:Platelet-Derived Growth Factor; D012176:Retinoids; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors; D004549:Elastin