Role of keratinocyte growth factor in the control of surfactant synthesis by fetal lung mesenchyme

Fetal lung maturation is regulated by mesenchymal-epithelial cell communica tion, which plays a major role in the control of surfactant synthesis by al veolar type II cells. We have recently shown that keratinocyte growth facto r (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 co ntrol of surfactant synthesis. Using a KGF-neutralizing antibody, we assess ed surfactant phospholipid synthesis by measuring choline incorporation int o disaturated phosphatidylcholine of isolated fetal type II cells. We found that KGF accounts for about half of the stimulating activity present in fe tal lung fibroblast-conditioned medium (FCM). By contrast, the use of an ep idermal growth factor-neutralizing antibody did not alter the FCM-stimulati ng activity. To further delineate KGF properties as a mesenchymal mediator, we wondered about its possibility to relay glucocorticoid-stimulating acti vity on the synthesis of the phospholipid moiety of surfactant in fetal lun g fibroblasts. A 24-h exposure to dexamethasone led us to detect a 50% incr ease in the level of KGF messenger RNA (mRNA) in isolated fetal lung fibrob lasts. Moreover, anti-KGF antibody totally abolished the further increase o f FCM-stimulating activity induced by dexamethasone. Thus, KGF seems to be a major player in mediating glucocorticoid stimulation of fetal lung matura tion.