Abstract
BackgroundThe 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.MethodsFortyseven cases of developing human lung including pseudoglandular, canalicular, saccular and alveolar periods were analyzed by immunohistochemisty for E- and N-cadherin and β-catenin and twentyone 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.ConclusionsE-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.
Highlights
The aim of this study was to analyze the cell-specific expression of E- and N-cadherin and b-catenin in developing human lung tissues from 12 to 40 weeks of gestation
The cadherin superfamily consists of several members and one of these, E-cadherin is expressed in epithelial cells and it is nowadays a commonly used marker of cell epithelial phenotype in studies focusing on the epithelial-mesenchymal transition (EMT) [8]
The cells underneath the epithelium, especially in smallest airways, showed nuclear positivity for b-catenin (Figure 1G), and in contrast, these non-epithelial cells at the same localizations seemed to be negative for E-and N-cadherin
Summary
The aim of this study was to analyze the cell-specific expression of E- and N-cadherin and b-catenin in developing human lung tissues from 12 to 40 weeks of gestation. The cadherin superfamily consists of several members and one of these, E-cadherin is expressed in epithelial cells and it is nowadays a commonly used marker of cell epithelial phenotype in studies focusing on the epithelial-mesenchymal transition (EMT) [8]. N-cadherin was originally found to be expressed in neural and muscle cells, but subsequently it is observed be an element of mesenchymal cells [9]. In studies investigating the EMT, N-cadherin has been used as a marker of mesenchymal differentiation [8]. Specific cadherins have been shown to directly stimulate cellular differentiation into certain types of tissue [10]. Expression of N-cadherin has been observed to be present in epithelial lung tumors in addition of E-cadherin and b-catenin [11]
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