Distinct Roles of Wnt/β-Catenin Signaling in the Pathogenesis of Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis.
Distinct Roles of Wnt/β-Catenin Signaling in the Pathogenesis of Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis.
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Wnt/β-连环蛋白信号传导在慢性阻塞性肺疾病和特发性肺纤维化发病机制中的独特作用
DOI：
10.1155/2017/3520581
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发表时间：
2017
影响因子：
4.6
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Shi J;Li F;Luo M;Wei J;Liu X
Wnt信号通路在生理条件下受到严格控制，在许多生物学功能中发挥关键作用，包括细胞命运规范和组织再生。近年来越来越多的证据表明，Wnt信号通路，尤其是Wnt/β-catenin信号通路的异常激活参与了慢性阻塞性肺疾病（COPD）和特发性肺纤维化（IPF）等慢性肺疾病的发病机制。在这方面，Wnt信号传导与其他细胞信号传导途径相互作用，以调节气道炎症和重塑、肺成肌纤维细胞增殖、上皮向间质转化（EMT）和肺气肿发展的起始和致病过程。有趣的是，Wnt/β-连环蛋白信号在IPF中被激活;在实验模型中，抑制该信号导致肺部炎症和纤维化减轻。相反，Wnt/β-连环蛋白信号传导在COPD组织中失活，并且其重新激活导致肺气肿模型中的空气空间扩大的改善，同时肺泡上皮结构和功能恢复。因此，这些研究暗示了Wnt/β-连环蛋白信号传导在这两种慢性肺部疾病发病机制中的不同机制，表明了COPD和IPF治疗的潜在靶点。本文综述了Wnt信号通路在COPD和IPF发病中的作用，重点阐述了Wnt/β-catenin信号通路在COPD和IPF发病中的作用机制和治疗靶点。
Wnt signaling pathways are tightly controlled under a physiological condition, under which they play key roles in many biological functions, including cell fate specification and tissue regeneration. Increasing lines of evidence recently demonstrated that a dysregulated activation of Wnt signaling, particularly the Wnt/β-catenin signaling, was involved in the pathogenesis of chronic pulmonary diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). In this respect, Wnt signaling interacts with other cellular signaling pathways to regulate the initiation and pathogenic procedures of airway inflammation and remodeling, pulmonary myofibroblast proliferation, epithelial-to-mesenchymal transition (EMT), and development of emphysema. Intriguingly, Wnt/β-catenin signaling is activated in IPF; an inhibition of this signaling leads to an alleviation of pulmonary inflammation and fibrosis in experimental models. Conversely, Wnt/β-catenin signaling is inactivated in COPD tissues, and its reactivation results in an amelioration of airspace enlargement with a restored alveolar epithelial structure and function in emphysema models. These studies thus imply distinct mechanisms of Wnt/β-catenin signaling in the pathogenesis of these two chronic pulmonary diseases, indicating potential targets for COPD and IPF treatments. This review article aims to summarize the involvement and pathogenic roles of Wnt signaling pathways in the COPD and IPF, with a focus on the implication of Wnt/β-catenin signaling as underlying mechanisms and therapeutic targets in these two incurable diseases.