Wu Min, Chen Jeng-Haur
College of Life Sciences, Zhejiang Normal University, Jinhua, Zhejiang, China.
Front Physiol. 2024 Apr 18;15:1385661. doi: 10.3389/fphys.2024.1385661. eCollection 2024.
Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel by genetic mutations causes the inherited disease cystic fibrosis (CF). CF lung disease that involves multiple disorders of epithelial function likely results from loss of CFTR function as an anion channel conducting chloride and bicarbonate ions and its function as a cellular regulator modulating the activity of membrane and cytosol proteins. In the absence of CFTR activity, abundant mucus accumulation, bacterial infection and inflammation characterize CF airways, in which inflammation-associated tissue remodeling and damage gradually destroys the lung. Deciphering the link between CFTR dysfunction and bacterial infection in CF airways may reveal the pathogenesis of CF lung disease and guide the development of new treatments. Research efforts towards this goal, including high salt, low volume, airway surface liquid acidosis and abnormal mucus hypotheses are critically reviewed.
基因突变导致的囊性纤维化跨膜传导调节因子(CFTR)阴离子通道功能障碍会引发遗传性疾病囊性纤维化(CF)。CF肺部疾病涉及上皮功能的多种紊乱,这可能是由于CFTR作为传导氯离子和碳酸氢根离子的阴离子通道的功能丧失,以及其作为调节膜蛋白和胞质蛋白活性的细胞调节因子的功能丧失所致。在缺乏CFTR活性的情况下,CF气道的特征是大量黏液积聚、细菌感染和炎症,其中与炎症相关的组织重塑和损伤会逐渐破坏肺部。解读CF气道中CFTR功能障碍与细菌感染之间的联系,可能会揭示CF肺部疾病的发病机制,并指导新治疗方法的开发。本文对为实现这一目标所做的研究工作进行了批判性综述,包括高盐、低容量、气道表面液体酸中毒和异常黏液假说。