Work

Prenatal, but Not Postnatal, Inhibition of Fibroblast Growth Factor Receptor Signaling Causes Emphysema

Year: 2002

Type: article

Abstract: 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.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.m208328200

Authors: Isamu Hokuto, Anne-Karina T. Perl, Jeffrey A. Whitsett

Institution: Cincinnati Children's Hospital Medical Center

Language: English

Topic: Neonatal Respiratory Health Research

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430