Oshika E, Liu S, Ung L P, Singh G, Shinozuka H, Michalopoulos G K, Katyal S L
Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
Pediatr Res. 1998 Mar;43(3):305-14. doi: 10.1203/00006450-199803000-00001.
In this study, we examined the effects of dexamethasone (DEX) on airway branching and subsequent lung maturation. DEX treatment of fetal rat lung explants was initiated during the early pseudoglandular stage of development. Day 14 fetal lung explants were cultured with and without DEX for 4 d. Explants treated with 10 nM or higher concentrations of DEX showed features of both distorted and accelerated maturation. DEX-treated lungs had growth retardation, distorted branching, dilated proximal tubules, and suppressed proliferation of epithelial cells of the distal tubules. Several biochemical and morphologic features of accelerated maturation were also observed: 1) the epithelial cells lining the distal tubules (prospective respiratory airways) were generally cuboidal or flattened; 2) the cuboidal cells often contained lamellar bodies and abundant glycogen; 3) rudimentary septa and large airspace were present; 4) mesenchymal tissue was attenuated and compressed between adjacent epithelial tubules; 5) the distribution of SP-C mRNA in distal tubules was more mature, with individual and clusters of cells expressing SP-C transcripts; and 6) the transcript levels of several genes related to epithelial growth [keratinocyte growth factor (KGF), KGF receptor, and hepatocyte growth factor receptor] and differentiation [surfactant proteins, SP-A, SP-B and SP-C and the Clara cell secretory protein, CC10] were precociously increased. These results show that DEX treatment of the lung during the early pseudoglandular stage accelerates the acquisition of several features of advanced maturation that normally accompany late stages of fetal development. We postulate that KGF mediates at least some effects of DEX on lung maturation and gene expression.
在本研究中，我们检测了地塞米松（DEX）对气道分支及随后肺成熟的影响。在发育的早期假腺泡阶段开始用地塞米松处理胎鼠肺组织块。将第14天的胎鼠肺组织块在有或无地塞米松的情况下培养4天。用10 nM或更高浓度地塞米松处理的组织块呈现出成熟扭曲和加速的特征。经地塞米松处理的肺组织生长迟缓、分支扭曲、近端小管扩张，远端小管上皮细胞增殖受抑制。还观察到一些加速成熟的生化和形态学特征：1）远端小管（未来的呼吸气道）内衬的上皮细胞通常为立方形或扁平状；2）立方形细胞常含有板层小体和丰富的糖原；3）存在原始的隔膜和大的气腔；4）间充质组织变薄并被相邻上皮小管之间压缩；5）远端小管中SP-C mRNA的分布更成熟，有单个细胞和细胞簇表达SP-C转录本；6）几种与上皮生长[角质形成细胞生长因子（KGF）、KGF受体和肝细胞生长因子受体]及分化[表面活性蛋白、SP-A、SP-B和SP-C以及克拉拉细胞分泌蛋白CC10]相关的基因的转录水平过早升高。这些结果表明，在早期假腺泡阶段用地塞米松处理肺可加速获得一些通常伴随胎儿发育后期的高级成熟特征。我们推测KGF介导了地塞米松对肺成熟和基因表达的至少部分作用。
