FGF signaling is required for pulmonary homeostasis following hyperoxia.
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.
Hokuto
Isamu
I
Cincinnati Children's Hospital Medical Center, Div. of Pulmonary Biology, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA. jett.whitsett@cchmc.org
Perl
Anne-Karina T
AK
Whitsett
Jeffrey A
JA
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
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