This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chelly, N. Articles by Bourbon, J. R. Search for Related Content PubMed PubMed Citation Articles by Chelly, N. Articles by Bourbon, J. R.

Role of Keratinocyte Growth Factor in the Control of Surfactant Synthesis by Fetal Lung Mesenchyme

INSERM Unit 319, Développement Normal et Pathologique des Fonctions Epitheliales, Université Paris 7-Denis Diderot, 75251 Paris, France

Address all correspondence and requests for reprints to: Jacques R. Bourbon, INSERM U319, Université Paris 7-Denis Diderot, Tour 33-43, Case courrier 7126, 2 Place Jussieu, 75251 Paris Cedex 05, France. E-mail: bourbon{at}paris7.jussieu.fr

Fetal lung maturation is regulated by mesenchymal-epithelial cell communication, which plays a major role in the control of surfactant synthesis by alveolar type II cells. We have recently shown that keratinocyte growth factor (KGF), also called fibroblast growth factor-7, enhances the maturation of fetal alveolar epithelial type II cells. Here, we investigated, among the factors produced by lung mesenchyme, the part attributable to KGF in the control of surfactant synthesis. Using a KGF-neutralizing antibody, we assessed surfactant phospholipid synthesis by measuring choline incorporation into disaturated phosphatidylcholine of isolated fetal type II cells. We found that KGF accounts for about half of the stimulating activity present in fetal lung fibroblast-conditioned medium (FCM). By contrast, the use of an epidermal growth factor-neutralizing antibody did not alter the FCM-stimulating activity. To further delineate KGF properties as a mesenchymal mediator, we wondered about its possibility to relay glucocorticoid-stimulating activity on the synthesis of the phospholipid moiety of surfactant in fetal lung fibroblasts. A 24-h exposure to dexamethasone led us to detect a 50% increase in the level of KGF messenger RNA (mRNA) in isolated fetal lung fibroblasts. Moreover, anti-KGF antibody totally abolished the further increase of FCM-stimulating activity induced by dexamethasone. Thus, KGF seems to be a major player in mediating glucocorticoid stimulation of fetal lung maturation.

This article has been cited by other articles:

				A. D. Bird, K. H. Tan, P. F. Olsson, M. Zieba, S. J. Flecknoe, D. R. Liddicoat, R. Mollard, S. B. Hooper, and T. J. Cole Identification of glucocorticoid-regulated genes that control cell proliferation during murine respiratory development J. Physiol., November 15, 2007; 585(1): 187 - 201. [Abstract] [Full Text] [PDF]

				P. R. Provost, M. Simard, and Y. Tremblay A Link between Lung Androgen Metabolism and the Emergence of Mature Epithelial Type II Cells Am. J. Respir. Crit. Care Med., August 1, 2004; 170(3): 296 - 305. [Abstract] [Full Text] [PDF]

				W. Raoul, B. Chailley-Heu, A.-M. Barlier-Mur, C. Delacourt, B. Maitre, and J. R. Bourbon Effects of vascular endothelial growth factor on isolated fetal alveolar type II cells Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1293 - L1301. [Abstract] [Full Text] [PDF]

				C. Danan, M.-L. Franco, P.-H. Jarreau, G. Dassieu, B. Chailley-Heu, J. Bourbon, and C. Delacourt High Concentrations of Keratinocyte Growth Factor in Airways of Premature Infants Predicted Absence of Bronchopulmonary Dysplasia Am. J. Respir. Crit. Care Med., May 15, 2002; 165(10): 1384 - 1387. [Abstract] [Full Text] [PDF]

				L. B. Ware and M. A. Matthay Keratinocyte and hepatocyte growth factors in the lung: roles in lung development, inflammation, and repair Am J Physiol Lung Cell Mol Physiol, May 1, 2002; 282(5): L924 - L940. [Abstract] [Full Text] [PDF]