Powell P P, Wang C C, Horinouchi H, Shepherd K, Jacobson M, Lipson M, Jones R
Molecular and Cell Biology Laboratory, Department of Anaesthesia and Critical Care Medicine, Massachusetts General Hospital-East, Boston, MA 02129, USA.
Am J Respir Cell Mol Biol. 1998 Oct;19(4):563-72. doi: 10.1165/ajrcmb.19.4.2994.
To characterize fibroblast growth factor (FGF) gene expression in the late fetal (days E18 to E22) and early postnatal lung (days P0 to P28), when the alveolar region undergoes extensive growth and reorganization, we analyzed the expression of four FGF receptors and six ligands. FGF receptor 1 (FGFR1) RNA levels were first low (E18) before rising late in the postnatal period (P28). FGFR2 RNA levels were detected early (at E18) and then increased (E20-P0) before falling (P2) to below later postnatal levels (P6 to P28). FGFR3 RNA levels were low at first (E18) and then increased, with peak levels in the days after birth (P2 to P10). FGFR4 RNA levels, barely detected in fetal lung (E18 to E22), increased at birth (P0) and remained high postnatally (P2 to P28). In fetal lung, FGF2 (basic FGF) RNA expression levels were low and FGF1 (acidic FGF) RNA levels were not detected: low RNA levels of each ligand were detected postnatally (P7 to P28). FGF3 to 5 and FGF7 RNA were not detected in fetal or postnatal lung. With in situ hybridization, predominantly the smooth muscle cells of large vessels expressed FGFR1 and 4 mRNA; the epithelial cells of large airways expressed FGFR1, 2, and 4; and alveolar cells expressed FGFR2, 3, and 4. Analysis of protein expression first identified FGF2 localized to the basement membrane of large airways and branching epithelial buds, to mesenchymal cells associated with buds, to the putative smooth muscle cells of large airways and vessels, and to pleural- and mesenchymal-associated cells (E18). Immediately before birth, this pattern of expression persisted (E20 to E22), with FGF2 also being expressed by putative smooth muscle cells of smaller airways and vessels (E22). After birth (P0 to P28), FGF2 expression remained relatively high in the smooth muscle cells of large and small vessels and in pleural cells; in airway smooth muscle cells and in most cells in the alveolar region, however, although FGF2 expression persisted in some cells, its intensity decreased with time.
为了描述在胎儿后期（胚胎期第18至22天）和出生后早期（出生后第0至28天）肺脏中，当肺泡区域经历广泛生长和重塑时成纤维细胞生长因子（FGF）基因的表达情况，我们分析了四种FGF受体和六种配体的表达。FGF受体1（FGFR1）的RNA水平起初较低（胚胎期第18天），随后在出生后期（出生后第28天）升高。FGFR2的RNA水平在早期（胚胎期第18天）被检测到，然后升高（胚胎期第20天至出生后第0天），之后下降（出生后第2天）至低于出生后期水平（出生后第6天至第28天）。FGFR3的RNA水平起初较低（胚胎期第18天），然后升高，在出生后的几天内达到峰值（出生后第2天至第10天）。FGFR4的RNA水平在胎儿肺脏中几乎检测不到（胚胎期第18天至22天），在出生时（出生后第0天）升高，并在出生后保持较高水平（出生后第2天至第28天）。在胎儿肺脏中，FGF2（碱性FGF）的RNA表达水平较低，未检测到FGF1（酸性FGF）的RNA水平：出生后（出生后第7天至第28天）检测到每种配体的RNA水平较低。在胎儿或出生后的肺脏中未检测到FGF3至5和FGF7的RNA。通过原位杂交，主要是大血管的平滑肌细胞表达FGFR1和4的mRNA；大气道的上皮细胞表达FGFR1、2和4；肺泡细胞表达FGFR2、3和4。蛋白质表达分析首先确定FGF2定位于大气道和分支上皮芽的基底膜、与芽相关的间充质细胞、大气道和血管的假定平滑肌细胞以及胸膜和间充质相关细胞（胚胎期第18天）。在即将出生前，这种表达模式持续存在（胚胎期第20天至22天），较小气道和血管的假定平滑肌细胞也表达FGF2（胚胎期第22天）。出生后（出生后第0天至第28天），FGF2在大小血管的平滑肌细胞和胸膜细胞中表达仍然相对较高；然而，在气道平滑肌细胞和肺泡区域的大多数细胞中，尽管FGF2在一些细胞中持续表达，但其强度随时间下降。
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