Shi Juan, Li Feng, Luo Meihui, Wei Jun, Liu Xiaoming
Center of Laboratory Medicine, General Hospital of Ningxia Medical University, Yinchuan 750004, China.
Institute of Human Stem Cell Research, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.
Mediators Inflamm. 2017;2017:3520581. doi: 10.1155/2017/3520581. Epub 2017 May 9.
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/-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/-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/-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/-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/-catenin signaling as underlying mechanisms and therapeutic targets in these two incurable diseases.
Wnt信号通路在生理条件下受到严格调控，在此条件下它们在许多生物学功能中发挥关键作用，包括细胞命运决定和组织再生。最近越来越多的证据表明，Wnt信号通路的失调激活，尤其是Wnt/β-连环蛋白信号通路，参与了慢性肺部疾病的发病机制，如慢性阻塞性肺疾病（COPD）和特发性肺纤维化（IPF）。在这方面，Wnt信号通路与其他细胞信号通路相互作用，以调节气道炎症和重塑、肺成肌纤维细胞增殖、上皮-间质转化（EMT）以及肺气肿发展的起始和致病过程。有趣的是，Wnt/β-连环蛋白信号通路在IPF中被激活；在实验模型中抑制该信号通路可减轻肺部炎症和纤维化。相反，Wnt/β-连环蛋白信号通路在COPD组织中失活，其重新激活可改善气腔扩大，恢复肺气肿模型中肺泡上皮的结构和功能。因此，这些研究暗示了Wnt/β-连环蛋白信号通路在这两种慢性肺部疾病发病机制中的不同作用机制，表明了COPD和IPF治疗的潜在靶点。这篇综述文章旨在总结Wnt信号通路在COPD和IPF中的参与情况和致病作用，重点关注Wnt/β-连环蛋白信号通路作为这两种不治之症潜在机制和治疗靶点的意义。
