Noncanonical Wnt planar cell polarity signaling in lung development and disease.
Noncanonical Wnt planar cell polarity signaling in lung development and disease.
复制标题
DOI：
10.1042/bst20190597
复制
发表时间：
2020-02-28
影响因子：
3.9
通讯作者：
Königshoff M
中科院分区：
文献类型：
--
作者：
Vladar EK;Königshoff M
平面细胞极性（PCP）信号通路是定向细胞行为（如迁移、不对称分裂和形态极化）的有效发育调节剂，这些定向细胞行为对于形成体轴和组织器官的复杂三维结构至关重要。PCP被认为是一种非经典Wnt途径，因为在经典Wnt级联中观察到的β-连环蛋白驱动的基因表达不存在的情况下，涉及Wnt配体和Frizzled家族受体。PCP机制的核心是蛋白质复合物，其能够在细胞内沿着沿着组织宽轴产生分子不对称性，这些不对称性被转化为极化肌动蛋白和微管细胞骨架动力学。五氯苯酚已成为呼吸系统发育、体内平衡和疾病过程的重要调节剂。它沿着其他信号通路起作用，通过控制细胞在分支形态发生过程中的定向扩张运动来产生肺的精细分支结构。PCP在气道上皮中起作用，以建立和维持呼吸纤毛沿着气道轴的取向，用于解剖学定向的粘膜纤毛清除。它还调节肺血管的建立。在成人组织中，PCP功能障碍与多种慢性肺部疾病有关，如囊性纤维化、慢性阻塞性肺病和特发性肺动脉高压，主要源于再生伤口愈合期间适当组织结构和功能的破坏以及异常细胞迁移。需要更好地了解这些（受损的）五氯苯酚机制，以充分利用针对慢性肺部疾病的五氯苯酚治疗机会。
The planar cell polarity (PCP) signaling pathway is a potent developmental regulator of directional cell behaviors such as migration, asymmetric division and morphological polarization that are critical for shaping the body axis and the complex three-dimensional architecture of tissues and organs. PCP is considered a noncanonical Wnt pathway due to the involvement of Wnt ligands and Frizzled family receptors in the absence of the beta-catenin driven gene expression observed in the canonical Wnt cascade. At the heart of the PCP mechanism are protein complexes capable of generating molecular asymmetries within cells along a tissue-wide axis that are translated into polarized actin and microtubule cytoskeletal dynamics. PCP has emerged as an important regulator of developmental, homeostatic and disease processes in the respiratory system. It acts along other signaling pathways to create the elaborately branched structure of the lung by controlling the directional protrusive movements of cells during branching morphogenesis. PCP operates in the airway epithelium to establish and maintain the orientation of respiratory cilia along the airway axis for anatomically directed mucociliary clearance. It also regulates the establishment of the pulmonary vasculature. In adult tissues, PCP dysfunction has been linked to a variety of chronic lung diseases such as cystic fibrosis, chronic obstructive pulmonary disease, and idiopathic pulmonary arterial hypertension, stemming chiefly from the breakdown of proper tissue structure and function and aberrant cell migration during regenerative wound healing. A better understanding of these (impaired) PCP mechanisms is needed to fully harness the therapeutic opportunities of targeting PCP in chronic lung diseases.
与终末期 IPAH 肺相比，肺血管重塑小鼠模型的基因表达分析。
影响因子：
5.8
作者：
Shimodaira K;Okubo Y;Ochiai E;Nakayama H;Katano H;Wakayama M;Shinozaki M;Ishiwatari T;Sasai D;Tochigi N;Nemoto T;Saji T;Kamei K;Shibuya K
通讯作者：
Shibuya K