Role of keratinocyte growth factor in the control of surfactant synthesis by fetal lung mesenchyme
Role of keratinocyte growth factor in the control of surfactant synthesis by fetal lung mesenchyme
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DOI：
10.1210/en.142.5.1814
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发表时间：
2001-05-01
期刊：
影响因子：
4.8
通讯作者：
Bourbon, JR
中科院分区：
文献类型：
--
作者：
Chelly, N;Henrion, A;Bourbon, JR
胎儿肺成熟受间充质-上皮细胞通讯的调控，而间充质-上皮细胞通讯在肺泡II型细胞合成表面活性剂的调控中起主要作用。我们最近发现，角质细胞生长因子（KGF），也称为成纤维细胞生长因子-7，可以促进胎儿肺泡上皮II型细胞的成熟。在肺间质产生的因子中，KGF对表面活性剂合成的控制作用进行了研究。使用kgf中和抗体，我们通过测定分离的胎儿II型细胞中胆碱并入不饱和磷脂酰胆碱来评估表面活性剂磷脂的合成。我们发现KGF约占胎儿肺成纤维细胞条件培养基（FCM）中刺激活性的一半。相比之下，使用表皮生长因子中和抗体并没有改变fcm刺激活性。为了进一步描述KGF作为间质介质的特性，我们想知道它是否可能在胎儿肺成纤维细胞中传递糖皮质激素刺激活性对表面活性剂磷脂部分合成的影响。暴露于地塞米松24小时后，我们检测到分离的胎儿肺成纤维细胞中KGF信使RNA （mRNA）水平增加了50%。抗kgf抗体完全消除了地塞米松诱导的fcm刺激活性的进一步升高。因此，KGF似乎是介导糖皮质激素刺激胎儿肺成熟的主要参与者。
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.