CFTR作为重症肺部感染的治疗靶点。

IF 3.6 2区 医学 Q1 PHYSIOLOGY
Jaime L Hook, Wolfgang M Kuebler
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引用次数: 0

摘要

肺部感染是全世界发病率和死亡率的主要原因之一。即使采用适当的抗生素和抗病毒治疗,住院患者的死亡率往往超过10%,这突出表明需要制定新的治疗策略。近年来,囊性纤维化跨膜传导调节剂(CFTR)除了在肺气道和肺外器官中的作用外,越来越被认为是肺泡稳态和防御的关键调节剂。在肺泡上皮中,CFTR介导肺泡液分泌和液体稳态;在微血管内皮中,CFTR维持血管屏障功能。CFTR还有助于肺泡免疫。然而,在肺部感染中,多种分子机制降低CFTR丰度并损害其功能,促进肺泡炎症、水肿和细胞死亡。因此,通过CFTR调节药物保存或恢复CFTR功能,以一种不依赖病原体的方式对抗肺部感染,是一种有希望的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CFTR as a therapeutic target for severe lung infection.

Lung infection is one of the leading causes of morbidity and mortality worldwide. Even with appropriate antibiotic and antiviral treatment, mortality in hospitalized patients often exceeds 10%, highlighting the need for the development of new therapeutic strategies. Of late, cystic fibrosis transmembrane conductance regulator (CFTR) is-in addition to its well-established roles in the lung airway and extrapulmonary organs-increasingly recognized as a key regulator of alveolar homeostasis and defense. In the alveolar epithelium, CFTR mediates alveolar fluid secretion and liquid homeostasis; in the microvascular endothelium, CFTR maintains vascular barrier function. CFTR also contributes to alveolar immunity. Yet, in lung infection, diverse molecular mechanisms reduce CFTR abundance and otherwise impair its function, promoting alveolar inflammation, edema, and cell death. Preservation or restoration of CFTR function by CFTR modulator drugs thus presents a promising avenue to combat lung infection in a pathogen-independent manner.

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来源期刊
CiteScore
9.20
自引率
4.10%
发文量
146
审稿时长
2 months
期刊介绍: The American Journal of Physiology-Lung Cellular and Molecular Physiology publishes original research covering the broad scope of molecular, cellular, and integrative aspects of normal and abnormal function of cells and components of the respiratory system. Areas of interest include conducting airways, pulmonary circulation, lung endothelial and epithelial cells, the pleura, neuroendocrine and immunologic cells in the lung, neural cells involved in control of breathing, and cells of the diaphragm and thoracic muscles. The processes to be covered in the Journal include gas-exchange, metabolic control at the cellular level, intracellular signaling, gene expression, genomics, macromolecules and their turnover, cell-cell and cell-matrix interactions, cell motility, secretory mechanisms, membrane function, surfactant, matrix components, mucus and lining materials, lung defenses, macrophage function, transport of salt, water and protein, development and differentiation of the respiratory system, and response to the environment.
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