Abstract
Lung diseases impact patients across the lifespan, from infants in the first minutes of life through the aged population. Congenital abnormalities of lung structure can cause lung disease at birth or make adults more susceptible to chronic disease. Continuous inhalation of atmospheric components also requires the lung to be resilient to cellular injury. Fibroblast growth factor 10 (FGF10) regulates multiple stages of structural lung morphogenesis, cellular differentiation, and the response to injury. As a driver of lung airway branching morphogenesis, FGF10 signaling defects during development lead to neonatal lung disease. Alternatively, congenital airway abnormalities attributed to FGF10 mutations increase the risk of chronic airway disease in adulthood. FGF10 also maintains progenitor cell populations in the airway and promotes alveolar type 2 cell expansion and differentiation following injury. Here we review the cellular and molecular mechanisms linking FGF10 to multiple lung diseases, from bronchopulmonary dysplasia in extremely preterm neonates, cystic fibrosis in children, and chronic adult lung disorders. Understanding the connections between FGF10 and lung diseases may lead to exciting new therapeutic strategies.
Highlights
Lung structure and physiology has remained consistent throughout mammalian evolution (Mess and Ferner, 2010)
In a pneumonectomy model of alveolar regeneration, interfering with FGFR2 signaling prevented myofibroblast differentiation (Chen et al, 2012). These observations could involve autocrine mechanisms where Fibroblast growth factors (FGFs) ligands including Fibroblast growth factor 10 (FGF10) directly regulate fibroblast phenotype or paracrine signaling loops involving Shh, Wnt, Bmp, or TGFβ signaling between adjacent cell populations
Inactivation of Hippo in smaller airways increases FGF10 expression in smooth muscle and leads to ectopic basal cell expansion. This highly regulated basal cell niche beautifully illustrates the paracrine nature of FGF10 signaling in maintaining normal lung biology throughout the lifespan
Summary
Congenital abnormalities of lung structure can cause lung disease at birth or make adults more susceptible to chronic disease. Fibroblast growth factor 10 (FGF10) regulates multiple stages of structural lung morphogenesis, cellular differentiation, and the response to injury. As a driver of lung airway branching morphogenesis, FGF10 signaling defects during development lead to neonatal lung disease. Congenital airway abnormalities attributed to FGF10 mutations increase the risk of chronic airway disease in adulthood. FGF10 maintains progenitor cell populations in the airway and promotes alveolar type 2 cell expansion and differentiation following injury. We review the cellular and molecular mechanisms linking FGF10 to multiple lung diseases, from bronchopulmonary dysplasia in extremely preterm neonates, cystic fibrosis in children, and chronic adult lung disorders. Understanding the connections between FGF10 and lung diseases may lead to exciting new therapeutic strategies
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