Lysosomal Acidification: A New Perspective on the Pathogenesis and Treatment of Pulmonary Fibrosis.

IF 4.2 2区 医学 Q1 PHYSIOLOGY
Kai Tian, Mengjiao Yu, Mengna Jiang, Zhengnan Gao, Dongnan Zheng, Weijian Shi, Demin Cheng, Xinyuan Zhao
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引用次数: 0

Abstract

Pulmonary fibrosis is a complex pathophysiological process characterized by local pulmonary inflammation and fibrosis, along with systemic inflammation and distal organ damage. The acidic environment of lysosomes, as intracellular degradation and recycling centers, is important for cellular homeostasis and function. This review summarizes the potential role of lysosomal acidification in pulmonary fibrosis pathogenesis and its implications for cross-organ effects. Various proteins and ion channels, such as V-ATPase, ClC-7, CFTR, TRPML1, and NHE, regulate lysosomal acidification. Lung fibrosis involves many cells, including lung epithelial cells, endothelial cells, macrophages, fibroblasts, and myofibroblasts. Studies have shown that abnormal lysosomal acidification significantly contributes to the onset and progression of pulmonary fibrosis. Damaged epithelial cells activate inflammatory and fibrotic signals through lysosomal dysfunction; abnormal lysosomal acidification in endothelial cells causes tissue edema and inflammatory responses; macrophages exacerbate inflammatory responses due to impaired lysosomal acidification; and fibroblasts hyperproliferate and transform into myofibroblasts due to deficient lysosomal acidification. Chronic pulmonary inflammation increases blood-gas barrier permeability, facilitating extravasation of inflammatory mediators (e.g., IL-6, TNF-α, and TGF-β) into the circulation, where they act as endocrine signals affecting distant organs. These findings provide a rationale for exploring novel therapeutic targets; future pharmacologic modulation of lysosomal acidification and inhibition of key inflammatory mediators may represent important strategies for preventing and treating pulmonary fibrosis and its systemic complications.

溶酶体酸化:肺纤维化发病机制和治疗的新视角。
肺纤维化是一个复杂的病理生理过程,以局部肺部炎症和纤维化为特征,并伴有全身炎症和远端器官损伤。溶酶体的酸性环境,作为细胞内降解和循环中心,对细胞的稳态和功能是重要的。本文综述了溶酶体酸化在肺纤维化发病机制中的潜在作用及其对跨器官效应的影响。多种蛋白和离子通道,如v - atp酶、ClC-7、CFTR、TRPML1和NHE,调节溶酶体酸化。肺纤维化涉及多种细胞,包括肺上皮细胞、内皮细胞、巨噬细胞、成纤维细胞和肌成纤维细胞。研究表明,异常溶酶体酸化对肺纤维化的发生和发展有重要作用。受损上皮细胞通过溶酶体功能障碍激活炎症和纤维化信号;内皮细胞溶酶体异常酸化导致组织水肿和炎症反应;巨噬细胞因溶酶体酸化受损而加剧炎症反应;由于溶酶体酸化不足,成纤维细胞过度增殖并转化为肌成纤维细胞。慢性肺部炎症增加血气屏障通透性,促进炎症介质(如IL-6、TNF-α和TGF-β)外渗进入循环,在循环中作为影响远端器官的内分泌信号。这些发现为探索新的治疗靶点提供了理论依据;未来对溶酶体酸化的药理学调节和对关键炎症介质的抑制可能是预防和治疗肺纤维化及其全身并发症的重要策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
10.50
自引率
0.00%
发文量
38
审稿时长
6-12 weeks
期刊介绍: Comprehensive Physiology is the most authoritative and comprehensive collection of physiology information ever assembled, and uses the most powerful features of review journals and electronic reference works to cover the latest key developments in the field, through the most authoritative articles on the subjects covered. This makes Comprehensive Physiology a valued reference work on the evolving science of physiology for both researchers and clinicians. It also provides a useful teaching tool for instructors and an informative resource for medical students and other students in the life and health sciences.
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