The asthma-related airway wall remodeling is associated i.a. with a damage of bronchial epithelium and subepithelial fibrosis. Functional interactions between human bronchial epithelial cells and human bronchial fibroblasts are known as the epithelial-mesenchymal trophic unit (EMTU) and are necessary for a proper functioning of lung tissue. However, a high concentration of the transforming growth factor-β1 (TGF-β1) in the asthmatic bronchi drives the structural disintegrity of epithelium with the epithelial-to-mesenchymal transition (EMT) of the bronchial epithelial cells, and of subepithelial fibrosis with the fibroblast-to-myofibroblast transition (FMT) of the bronchial fibroblasts. Since previous reports indicate different intrinsic properties of the human bronchial epithelial cells and human bronchial fibroblasts which affect their EMT/FMT potential beetween cells derived from asthmatic and non-asthmatic patients, cultured separatelly in vitro, we were interested to see whether corresponding effects could be obtained in a co-culture of the bronchial epithelial cells and bronchial fibroblasts. In this study, we investigate the effects of the TGF-β1 on the EMT markers of the bronchial epithelial cells cultured in the air-liquid-interface and effectiveness of FMT in the bronchial fibroblast populations in the EMTU models. Our results show that the asthmatic co-cultures are more sensitive to the TGF-β1 than the non-asthmatic ones, which is associated with a higher potential of the asthmatic bronchial cells for a profibrotic response, analogously to be observed in '2D' cultures. They also indicate a noticeable impact of human bronchial epithelial cells on the TGF-β1-induced FMT, stronger in the asthmatic bronchial fibroblast populations in comparison to the non-asthmatic ones. Moreover, our results suggest the protective effects of fibroblasts on the structure of the TGF-β1–exposed mucociliary differentiated bronchial epithelial cells and their EMT potential. Our data are the first to demonstrate a protective effect of the human bronchial fibroblasts on the properties of the human bronchial epithelial cells, which suggests that intrinsic properties of not only epithelium but also subepithelial fibroblasts affect a proper condition and function of the EMTU in both normal and asthmatic individuals.

中文翻译：

---

哮喘和非哮喘供体的人支气管成纤维细胞和上皮细胞对上皮-间充质营养单位模型中转化生长因子-β1的反应性

哮喘相关的气道壁重塑与支气管上皮损伤和上皮下纤维化有关。人支气管上皮细胞和人支气管成纤维细胞之间的功能相互作用被称为上皮间充质营养单位 (EMTU)，是肺组织正常运作所必需的。然而，哮喘支气管中高浓度的转化生长因子-β1 (TGF-β1) 驱动上皮细胞结构解体，支气管上皮细胞的上皮间质转化 (EMT)，以及上皮下纤维化和支气管成纤维细胞的成纤维细胞-肌成纤维细胞转化（FMT）。由于先前的报告表明，人支气管上皮细胞和人支气管成纤维细胞的不同内在特性会影响它们在来自哮喘和非哮喘患者的细胞之间的 EMT/FMT 潜能，分别在体外培养，我们有兴趣看看是否可以产生相应的影响在支气管上皮细胞和支气管成纤维细胞的共培养物中获得。在这项研究中，我们研究了 TGF-β1 对气液界面中培养的支气管上皮细胞 EMT 标志物的影响以及 FMT 在 EMTU 模型中支气管成纤维细胞群中的有效性。我们的结果表明，哮喘共培养物比非哮喘共培养物对 TGF-β1 更敏感，这与哮喘支气管细胞促纤维化反应的更高潜力有关，类似于在“2D”培养物中观察到的。他们还表明人支气管上皮细胞对 TGF-β1 诱导的 FMT 有显着影响，与非哮喘患者相比，哮喘支气管成纤维细胞群的影响更强。此外，我们的结果表明成纤维细胞对暴露于 TGF-β1 的黏液纤毛分化支气管上皮细胞的结构及其 EMT 潜力具有保护作用。我们的数据首次证明了人支气管成纤维细胞对人支气管上皮细胞特性的保护作用，