Prenatal, but not postnatal, inhibition of fibroblast growth factor receptor signaling causes emphysema.
Although fibroblast growth factor (FGF) signaling is required for the formation of the lung in the embryonic period, it is unclear whether FGF receptor activity influences lung morphogenesis later in development. We generated transgenic mice expressing a soluble FGF receptor (FGFR-HFc) under conditional control of the lung-specific surfactant protein C promoter (SP-C-rtTA), to inhibit FGF activity at various times in late gestation and postnatally. Although expression of FGFR-HFc early in development caused severe fetal lung hypoplasia, activation of the transgene in the postnatal period did not alter alveolarization, lung size, or histology. In contrast, expression of the transgene at post-conception day E14.5 decreased lung tubule formation before birth and caused severe emphysema at maturity. FGFR-HFc caused mild focal emphysema when expressed from E16.5 but did not alter alveolarization when expressed after birth. Although FGF signaling was required for branching morphogenesis early in lung development, postnatal alveolarization was not influenced by FGFR-HFc.
Hokuto
Isamu
I
Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Perl
Anne-Karina T
AK
Whitsett
Jeffrey A
JA
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D002454:Cell Differentiation / Q000502:physiology; D046508:Culture Techniques; D004318:Doxycycline / Q000494:pharmacology; D005333:Fetus; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005865:Gestational Age; D008168:Lung / Q000196:embryology* / Q000473:pathology / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D011401:Promoter Regions, Genetic; D011656:Pulmonary Emphysema / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics; D011663:Pulmonary Surfactants / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D015415:Biomarkers; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; D004318:Doxycycline