甲状腺转录因子-1在人胎肺和新生儿肺上皮细胞中的时序表达

Temporal expression of thyroid transcription factor-1 in fetal and neonatal human lungs

摘要:

目的：甲状腺转录因子1(TTF1)作为重要的调控上皮细胞特异性基因表达的同源核转录因子,对促进胎肺发育起重要作用。TTF1在人胎肺发育过程中的表达规律尚不清楚。该文旨在检测TTF1在人胎肺发育过程中的时序表达,探讨其在胎肺上皮细胞发育、分化过程中的调控作用。方法：由孕妇自愿捐献的胎龄为10～27周胎肺组织32例及死亡新生儿正常肺组织7例(28～36周),用免疫组织化学技术检测TTF1的表达。结果：TTF1在胎肺第10周已开始表达,定位于上皮细胞核内,在远端呼吸道上皮表达丰富;随着支气管的发育分化,TTF1阳性细胞散在分布于支气管上皮中的无纤毛细胞,在远端支气管上皮细胞核中强表达,尤其是在新生支气管芽的尖端;在胎肺发育末期及新生儿肺中,TTF1阳性反应在Ⅱ型肺泡上皮细胞和肺泡前体细胞中稳定表达,纤毛细胞和Ⅰ型肺泡上皮细胞无表达。结论：TTF1参与支气管树形态发生和肺泡的发育成熟,并调控Ⅱ型肺泡上皮细胞及肺泡前体细胞分泌肺表面活性物质,与适应出生后执行功能的需要密切相关。

Abstract:

OBJECTIVE: Recent progress in developmental biology has shown that the thyroid transcription factor-1 (TTF-1) plays an important role in lung development. The aim of this study was to investigate the expression and distribution of TTF-1 and its function during the development of epithelial stem cells in fetal human lungs. METHODS: Human lung tissues were obtained with parental consent from 32 fetuses (10-27 weeks) and from seven newborn infants (28-36 weeks) who had not died from pulmonary diseases. The expression of TTF-1 was examined by immunohistochemistry. RESULTS: TTF-1 was expressed in the nuclei of columnar nonciliated epithelial cells of the fetal human lung as early as 10 weeks of gestation. With the development of bronchus TTF-1 positive cells were present in scattered nonciliated cells and were predominantly expressed in the nuclei of epithelial cells of the distal tubules and lung buds. By the late phase of fetal development or neonatal period, TTF-1 was expressed in only type Ⅱ alveolar epithelium cells and their precursor cells,but was absent in ciliated cells and type Ⅰ alveolar epithelium cells. CONCLUSIONS: TTF-1 can stimulate the growth of both bronchial trees and alveolar cells and regulate the type Ⅱ alveolar epithelium cells and their precursors to secret surfactants.