Rimessi Alessandro, Vitto Veronica A M, Patergnani Simone, Pinton Paolo
Department of Medical Sciences and Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
Center of Research for Innovative Therapies in Cystic Fibrosis, University of Ferrara, Ferrara, Italy.
Front Pharmacol. 2021 Mar 11;12:581645. doi: 10.3389/fphar.2021.581645. eCollection 2021.
Cystic fibrosis (CF) is an autosomal recessive disorder characterized by mutations in the cystic fibrosis transmembrane conductance regulator gene, which causes multifunctional defects that preferentially affect the airways. Abnormal viscosity of mucus secretions, persistent pathogen infections, hyperinflammation, and lung tissue damage compose the classical pathological manifestation referred to as CF lung disease. Among the multifunctional defects associated with defective CFTR, increasing evidence supports the relevant role of perturbed calcium (Ca) signaling in the pathophysiology of CF lung disease. The Ca ion is a critical player in cell functioning and survival. Its intracellular homeostasis is maintained by a fine balance between channels, transporters, and exchangers, mediating the influx and efflux of the ion across the plasma membrane and the intracellular organelles. An abnormal Ca profile has been observed in CF cells, including airway epithelial and immune cells, with heavy repercussions on cell function, viability, and susceptibility to pathogens, contributing to proinflammatory overstimulation, organelle dysfunction, oxidative stress, and excessive cytokines release in CF lung. This review discusses the role of Ca signaling in CF and how its dysregulation in airway epithelial and immune cells contributes to hyperinflammation in the CF lung. Finally, we provide an outlook on the therapeutic options that target the Ca signaling to treat the CF lung disease.
囊性纤维化（CF）是一种常染色体隐性疾病，其特征在于囊性纤维化跨膜传导调节因子基因突变，该突变会导致多种功能缺陷，优先影响气道。黏液分泌物异常黏稠、持续性病原体感染、过度炎症反应和肺组织损伤构成了被称为CF肺部疾病的经典病理表现。在与缺陷性CFTR相关的多种功能缺陷中，越来越多的证据支持钙（Ca）信号紊乱在CF肺部疾病病理生理学中的相关作用。钙离子在细胞功能和存活中起着关键作用。其细胞内稳态通过通道、转运体和交换体之间的精细平衡来维持，这些通道、转运体和交换体介导离子跨质膜和细胞内细胞器的流入和流出。在CF细胞中，包括气道上皮细胞和免疫细胞，已观察到异常的钙分布，这对细胞功能、活力和病原体易感性产生重大影响，导致CF肺部出现促炎过度刺激、细胞器功能障碍、氧化应激和细胞因子过度释放。本综述讨论了钙信号在CF中的作用，以及其在气道上皮细胞和免疫细胞中的失调如何导致CF肺部的过度炎症反应。最后，我们展望了针对钙信号治疗CF肺部疾病的治疗选择。
