Conditional expression of fibroblast growth factor-7 in the developing and mature lung
Conditional expression of fibroblast growth factor-7 in the developing and mature lung
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DOI：
10.1074/jbc.275.16.11858
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发表时间：
2000-04-21
影响因子：
4.8
通讯作者：
Whitsett, JK
中科院分区：
文献类型：
--
作者：
Tichelaar, JW;Lu, W;Whitsett, JK
在人肺表面活性蛋白-C(SP-C)或大鼠Clara细胞分泌蛋白(CCSP)基因调控元件的控制下，人成纤维细胞生长因子-7(FGF-7)在转基因小鼠中对肺形态发生、呼吸道上皮细胞分化和增殖的影响进行了研究。多西环素诱导胎肺呼吸上皮细胞表达成纤维细胞生长因子-7。在产前，在Sp-c和CCSP转基因系中，多西环素诱导呼吸道上皮细胞中的成纤维细胞生长因子-7mRNA，增加肺大小并引起囊腺瘤样畸形。出生后，CCSP-RTTA和(Teto)(7)-CMV-FGF-7转基因小鼠均存活，肺组织形态正常。强力霉素诱导CCSP-RTTA(Teto)(7)-CMV-FGF-7小鼠肺上皮细胞明显增殖，腺瘤样增生，肺内单个核细胞浸润。去多西环素后，成纤维细胞生长因子-7引起的上皮细胞增生基本消失。多西环素有条件地诱导肺表面活性蛋白、TTF-1和水通道蛋白5的表达。Sp-c-RTTA和CCSP-RTTA激活剂小鼠提供了在发育和成熟的肺中有条件地控制呼吸道上皮细胞表达的模型，改变了肺的形态发生、分化和增殖。
Effects of fibroblast growth factor-7 (FGF-7) on lung morphogenesis, respiratory epithelial cell differentiation, and proliferation mere assessed in transgenic mice in which the human FGF-7 cDNA was controlled by a conditional promoter under the direction of regulatory elements from either the human surfactant protein-C (SP-C) or rat Clara cell secretory protein (ccsp) genes. Expression of FGF-7 was induced in respiratory epithelial cells of the fetal lung by administration of doxycycline to the dam. Prenatally, doxycycline induced FGF-7 mRNA in respiratory epithelial cells in both Sp-c and Ccsp transgenic lines, increasing lung size and causing cystadenomatoid malformation. Postnatally, mice bearing both Ccsp-rtta and (Teto)(7)-cmv-fgf-7 transgenes survived, and lung morphology was normal, Induction of FGF-7 expression by doxycycline in the Ccsp-rtta x (Teto)(7)-cmv-fgf-7 mice caused marked epithelial cell proliferation, adenomatous hyperplasia, and pulmonary infiltration with mononuclear cells. Epithelial cell hyperplasia caused by FGF-7 was largely resolved after removal of doxycycline. Surfactant proteins, TTF-1, and aquaporin 5 expression were conditionally induced by doxycycline. The Sp-c-rtta and Ccsp-rtta activator mice provide models in which expression is conditionally controlled in respiratory epithelial cells in the developing and mature lung, altering lung morphogenesis, differentiation, and proliferation.