Tissue remodelling in chronic bronchial diseases: from the epithelial to mesenchymal phenotype.
Tissue remodelling in chronic bronchial diseases: from the epithelial to mesenchymal phenotype.
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DOI：
10.1183/09059180.00004413
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发表时间：
2014-03-01
影响因子：
7.5
通讯作者：
Magnan, Antoine
中科院分区：
文献类型：
--
作者：
Pain, Mallory;Bermudez, Olga;Lacoste, Philippe;Royer, Pierre-Joseph;Botturi, Karine;Tissot, Adrien;Brouard, Sophie;Eickelberg, Oliver;Magnan, Antoine
气道重塑是慢性支气管疾病的关键特征，其特征在于上皮细胞的异常修复和成纤维细胞的积聚，这有助于细胞外基质（ECM）沉积，导致固定的支气管阻塞。最近，上皮间质转化（EMT）已被确定为一个新的来源的成纤维细胞，可能有助于气道重塑。这种现象由支气管上皮细胞的上皮表型的丧失和间充质表型的获得组成。然后这些细胞能够迁移并分泌ECM分子。在此，我们回顾不同类型的EMT。然后，我们将重点关注所涉及的信号通路，如转化生长因子-β和Wnt，以及最近描述的Sonic Hedgehog通路。最后，我们将强调EMT在特定慢性支气管病变（如哮喘、慢性阻塞性肺疾病和肺移植后闭塞性细支气管炎）气道重塑中的意义。尽管体外模型的局限性，EMT在体内的未来研究是必要的，以阐明支气管阻塞的病理机制。
Airway remodelling is a critical feature of chronic bronchial diseases, characterised by aberrant repair of the epithelium and accumulation of fibroblasts, which contribute to extracellular matrix (ECM) deposition resulting in fixed bronchial obstruction. Recently, epithelial–mesenchymal transition (EMT) has been identified as a new source of fibroblasts that could contribute to the remodelling of the airways. This phenomenon consists of the loss of the epithelial phenotype by bronchial epithelial cells and the acquisition of a mesenchymal phenotype. These cells are then able to migrate and secrete ECM molecules. Herein, we review the different types of EMT. We will then focus on the signalling pathways that are involved, such as transforming growth factor-β and Wnt, as well as the more recently described Sonic Hedgehog pathway. Finally, we will highlight the implication of EMT in airway remodelling in specific chronic bronchial pathologies, such as asthma, chronic obstructive pulmonary disease and bronchiolitis obliterans following lung transplantation. Despite the limitations of in vitro models, future studies of EMT in vivo are warranted to shed new light on the pathomechanisms of bronchial obstruction.