Journal article
Keratinocyte growth factor stimulates CFTR-independent fluid secretion in the fetal lung in vitro
American journal of physiology. Lung cellular and molecular physiology, Vol.271(6), pp.L987-L994
12/01/1996
DOI: 10.1152/ajplung.1996.271.6.L987
PMID: 8997270
Abstract
Keratinocyte growth factor (KGF) caused cystic dilation of mouse fetal lung explants in vitro, markedly increasing the luminal volume of lung buds and disrupting branching morphogenesis. Effects of KGF were dose dependent, were detected within 4 h of treatment, and were blocked by cycloheximide but not by actinomycin D, indicating that de novo protein synthesis mediated the response. Effects of KGF were inhibited by bumetanide, an inhibitor of the Na(+)-K(+)-Cl- cotransporter, and ouabain, an inhibitor of the Na(+)-K(+)-ATPase. KGF stimulated fluid secretion equally in lung buds from cystic fibrosis transmembrane conductance regulators (CFTR) -/- and wild-type embryos, indicating that the effects were mediated by CFTR-independent Cl- transport. Microelectrode studies demonstrated that, whereas KGF did not acutely alter the transepithelial potential difference (PD) across the respiratory epithelium, the PD decreased while luminal volume increased during chronic exposure. KGF inhibited expression of alpha-subunit of epithelial Na+ channel (alpha-ENaC) mRNA, suggesting that KGF may inhibit Na+ absorption, which may contribute to KGF-induced fluid accumulation. KGF-induced fluid accumulation is driven by CFTR-independent Cl- transport and associated with decreased expression of alpha-ENaC.
Details
- Title: Subtitle
- Keratinocyte growth factor stimulates CFTR-independent fluid secretion in the fetal lung in vitro
- Creators
- L Zhou - Division of Pulmonary Biology, Children's Hospital Medical Center,Cincinnati, Ohio 45229-3039, USAP. B McCray - Division of Pulmonary Biology, Children's Hospital Medical Center,Cincinnati, Ohio 45229-3039, USAR. W Graeff - Division of Pulmonary Biology, Children's Hospital Medical Center,Cincinnati, Ohio 45229-3039, USAW. S Simonet - Division of Pulmonary Biology, Children's Hospital Medical Center,Cincinnati, Ohio 45229-3039, USAJ. A Whitsett - Division of Pulmonary Biology, Children's Hospital Medical Center,Cincinnati, Ohio 45229-3039, USA
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Lung cellular and molecular physiology, Vol.271(6), pp.L987-L994
- DOI
- 10.1152/ajplung.1996.271.6.L987
- PMID
- 8997270
- ISSN
- 1040-0605
- eISSN
- 1522-1504
- Language
- English
- Date published
- 12/01/1996
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984093319402771
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