Growth factors and fetal lung development mediated by mechanical forces

Incomplete development of the lung secondary to extreme prematurity or pulmonary hypoplasia causes significant morbidity and mortality during the neonatal period. Currently, the management is primarily supportive with no specific treatment to stimulate the growth and development of the lung. Mechanical forces generated inside the fetal lung by constant distention pressure and "breathing-like movements" are a major determinant of fetal lung development. However, the mechanisms by which lung cells sense these mechanical signals to promote lung development are not well-defined. Tracheal ligation has been used not only experimentally but also in human fetuses affected by severe congenital diaphragmatic hernia to stimulate lung growth and decrease the degree of pulmonary hypoplasia. Past investigations suggested that the increase of intratracheal pressure after tracheal ligation releases soluble factors that are critical for lung development. Studies from our laboratory have shown that mechanical strain of fetal type Ⅱ epithelial cells, simulating mechanical forces in utero, promotes differentiation via release of epidermal growth factor receptor ligands heparin binding epidermal growth factor-like growth factor and transforming growth factor alpha. The identification of growth factors released by mechanical forces that are importantfor normal lung development could lead to novel treatments to accelerate lung development.