Kaarteenaho Riitta, Lappi-Blanco Elisa, Lehtonen Siri
Institute of Clinical Medicine, Department of Internal Medicine/Respiratory Research Unit, Centre of Excellence in Research, University of Oulu and Oulu University Hospital, Oulu, Finland.
BMC Dev Biol. 2010 Nov 16;10:113. doi: 10.1186/1471-213X-10-113.
The aim of this study was to analyze the cell-specific expression of E- and N-cadherin and β-catenin in developing human lung tissues from 12 to 40 weeks of gestation.
Forty-seven cases of developing human lung including pseudoglandular, canalicular, saccular and alveolar periods were analyzed by immunohistochemistry for E- and N-cadherin and β-catenin and twenty-one cases were also investigated by RT-PCR for E- and N-cadherin and β-catenin. For identifying the lung cells, the sections were also stained with antibodies against thyroid transcription factor-1 (TTF-1) and caveolin-1. Normal adult lung tissue was used as a control. E-cadherin was strongly expressed in epithelium of bronchi and large bronchioles from week 12 onwards and it was also positive in alveoli in pretype II cells and type II cells. N-cadherin was present in most of the epithelial cells of bronchi and the largest bronchioles during the pseudo-glandular and canalicular periods. N-cadherin was not detected in epithelium of developing alveoli. β-catenin was strongly membrane-bound and positively expressed in bronchial epithelium from week 12 to week 40; it showed nuclear positivity in both developing airway epithelium and in the cells underneath the epithelium during pseudo-glandular period and to a lesser degree also in the canalicular period. β-catenin was positive in pretype II cells as well as in type I and type II pneumocytes within alveoli. RT-PCR analyses revealed detectable amounts of RNAs of E- and N-cadherin and β-catenin in all cases studied. The amounts of RNAs were higher in early stages of gestation.
E-cadherin is widely expressed in bronchial and alveolar epithelial cells. N-cadherin exhibit extensive epithelial positivity in bronchial epithelial cells during early lung development. The presence of β-catenin was observed in several cell types with a distinct location in tissue and cells in various gestational stages, indicating that it possesses several roles during lung development. The expressions of protein and mRNAs of E- and N-cadherin and β-catenin were higher in early gestation compared to of the end. Moreover, the expressions of these factors were higher during the lung development than in the adult human lung.
本研究旨在分析妊娠12至40周人发育肺组织中E-钙黏蛋白、N-钙黏蛋白和β-连环蛋白的细胞特异性表达。
采用免疫组织化学方法对47例包括假腺期、小管期、囊状期和肺泡期的人发育肺组织进行E-钙黏蛋白、N-钙黏蛋白和β-连环蛋白分析,同时采用RT-PCR方法对21例进行E-钙黏蛋白、N-钙黏蛋白和β-连环蛋白检测。为鉴定肺细胞,切片还用抗甲状腺转录因子-1(TTF-1)和小窝蛋白-1抗体染色。正常成人肺组织作为对照。从妊娠12周起,E-钙黏蛋白在支气管和大支气管上皮中强烈表达,在II型前体细胞和II型细胞的肺泡中也呈阳性。在假腺期和小管期,N-钙黏蛋白存在于支气管和最大支气管的大多数上皮细胞中。在发育中的肺泡上皮中未检测到N-钙黏蛋白。β-连环蛋白在12周至40周的支气管上皮中强烈膜结合且呈阳性表达;在假腺期,其在发育中的气道上皮及其下方细胞中均显示核阳性,在小管期程度较轻。β-连环蛋白在II型前体细胞以及肺泡内的I型和II型肺细胞中呈阳性。RT-PCR分析显示,在所有研究病例中均检测到E-钙黏蛋白、N-钙黏蛋白和β-连环蛋白的RNA。RNA量在妊娠早期较高。
E-钙黏蛋白在支气管和肺泡上皮细胞中广泛表达。在肺发育早期,N-钙黏蛋白在支气管上皮细胞中呈现广泛的上皮阳性。在不同妊娠阶段的组织和细胞中,多种细胞类型中均观察到β-连环蛋白的存在,且其定位不同,表明其在肺发育过程中具有多种作用。与妊娠末期相比,E-钙黏蛋白、N-钙黏蛋白和β-连环蛋白的蛋白质和mRNA表达在妊娠早期较高。此外,这些因子在肺发育过程中的表达高于成人肺组织。