Growth factors in the fetal and neonatal lung

Abstract

Formation and orderly development of the mammalian lung results from a complex set of cell to cell and cell to matrix interactions following transcriptional regulation during pulmonary organogenesis. Transcriptional control of differentiation genes early on and epithelial-mesenchymal interactions mediated by growth factors later on, resulting in the formation of conducting airways and an extensive alveolar capillary interface, is critical for normal lung development. HNF-3beta and TTF-1 are transcription factors that are involved in gene regulation and formation and differentiation of respiratory epithelium. Studies done in early mouse embryonic lung demonstrate that a variety of peptide growth factors and their receptors are expressed early on in lung development. Signalling through the FGFR2 is critical to normal development of the distal epithelium and mesenchyme. The inductive and permissive influences of growth factors on lung development has been demonstrated by gain or loss of function experiments in early embryonic mouse lung organ culture, in transgenic and in null mutant mice. VEGF present in airway epithelial cells is involved in the maturation as well as proliferation of capillary endothelial cells. Epithelial-endothelial interactions during lung development are important in establishing a functional blood gas interface. Epithelial-mesenchymal interactions mediated by growth factors are also important in the restoration of normal alveolar architecture after lung injury. Further understanding of the role of these growth factors and their cellular interactions in bronchopulmonary dysplasia and in tissue repair following lung injury, may lead to development of better therapeutic modalities in treating these disorders.

Response of vascular endothelial growth factor and angiogenesis-related genes to stepwise increases in inspired oxygen in neonatal rat lungs

“…Microvascular development, which is essential for efficient gas exchange, is regulated by vascular endothelial growth factor (VEGF), which has been shown to be disrupted in BPD (12)(13)(14). Exposure to high concentrations of oxygen during lung development results in lung injury characterized by alterations in capillary density, endothelial cell destruction, pulmonary inflammation, and inhibition of the process of alveolarization (15)(16)(17)(18)(19).…”

“…VEGF is a potent, endothelial cell mitogen that stimulates vessel proliferation, migration, and tube formation leading to angiogenic growth of new blood vessels (15)(16)(17)(18)(19). It is essential for angiogenesis during development; the deletion of a single allele arrests angiogenesis and causes embryonic lethality (20)(21)(22).…”

Effects of Positive End-Expiratory Pressure, Inhaled Nitric Oxide and Surfactant on Expression of Proinflammatory Cytokines and Growth Factors in Preterm Piglet Lungs

“…PDGF-B and IGF-I are the important GFs in lung development (18). PDGF-B is a chemotactic factor for monocytes and granulocytes during inflammation and overexpression of PDGF-B induce inflammatory injury (19), whereas IGF signaling pathway plays a critical role in proliferation and differentiation of alveolar epithelium during tissue remodeling and repair (20).…”

Misplaced pulmonary arteries in an adult patient with pulmonary hypertension

“…A mutation or insult during embryogenesis to the governing mechanism for angiogenesis has been suggested in cases of MLV without ACD [2,20]. Vascular endothelial growth factors have also been implicated as a potential mechanism [24,25]. Arterial muscularisation may be a primary anomaly related to abnormal vascular development [26] or secondary to regional hypoxaemia resulting from intrapulmonary shunting via gas exchange through the arteriovenular wall [19,27].…”