title: FGF signaling is required for pulmonary homeostasis following hyperoxia.
abstract: To assess the role of fibroblast growth factor (FGF) signaling in pulmonary function in the postnatal period, we generated transgenic mice in which a soluble FGF receptor (FGFR-HFc) was conditionally expressed in respiratory epithelial cells of the mouse lung, thereby inhibiting FGF activity. Although FGFR-HFc did not alter postnatal lung morphogenesis, male FGFR-HFc transgenic mice were more susceptible to hyperoxia and failed to recover when ambient oxygen concentrations were normalized. Inflammation, alveolar-capillary leak, and mortality were increased following exposure to 95% Fi(O(2)). Expression of surfactant protein (SP)-A and SP-B were significantly decreased in association with decreased immunostaining for thyroid transcription factor-1. FGF signaling is required for maintenance of surfactant homeostasis and lung function during hyperoxia in vivo, mediated, at least in part, by its role in the maintenance of SP-B expression.
authors: Cincinnati Children's Hospital Medical Center, Div. of Pulmonary Biology, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA. jett.whitsett@cchmc.org
authors: Isamu
authors: I
authors: Hokuto
authors: Anne-Karina T
authors: AK
authors: Perl
authors: Jeffrey A
authors: JA
authors: Whitsett
mesh_terms: D000367:Age Factors; D000818:Animals; D002199:Capillary Permeability / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D018496:Hyperoxia / Q000378:metabolism* / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010100:Oxygen / Q000633:toxicity; D011014:Pneumonia / Q000378:metabolism / Q000503:physiopathology; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics* / Q000378:metabolism*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D011663:Pulmonary Surfactants; D017468:Receptors, Fibroblast Growth Factor; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D010100:Oxygen