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探讨 Notch 信号通路在肺部疾病发展中的作用。

Examining the contribution of Notch signaling to lung disease development.

机构信息

Center for Vascular and Heart Research, Fralin Biomedical Research Institute, Virginia Tech, Roanoke, VA, 24016, USA.

Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta, 34518, Egypt.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2024 Sep;397(9):6337-6349. doi: 10.1007/s00210-024-03105-8. Epub 2024 Apr 23.

Abstract

Notch pathway is a widely observed signaling system that holds pivotal functions in regulating various developmental cellular functions and operations. The Notch signaling mechanism is crucial for lung homeostasis, damage, and restoration. Based on increasing evidence, the Notch pathway has been identified, as critical for fibrosis and subsequently, the development of chronic fibroproliferative conditions in various organs and tissues. Recent research indicates that deregulation of Notch signaling correlates with the pathogenesis of significant pulmonary conditions, particularly chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, asthma, pulmonary arterial hypertension (PAH), lung carcinoma, and pulmonary abnormalities in some hereditary disorders. In various cellular and tissue environments, and across both physiological and pathological conditions, multiple consequences of Notch activation have been observed. Studies have ascertained that the Notch signaling cascade exhibits close associations with various other signaling systems. This study provides an updated overview of Notch signaling's role, especially its link to fibrosis and its potential therapeutic implications. This study sheds light on the latest findings regarding the mechanisms and outcomes of irregular or lacking Notch activity in the onset and development of pulmonary diseases. As our insight into this signaling mechanism suggests that modulating Notch signaling might hold potential as a valuable additional therapeutic approach in upcoming research.

摘要

Notch 通路是一种广泛存在的信号系统,在调节各种发育细胞功能和操作中起着关键作用。Notch 信号机制对于肺稳态、损伤和修复至关重要。基于越来越多的证据, Notch 通路已被确定为纤维化的关键,随后在各种器官和组织中慢性纤维增生性疾病的发展中也起着关键作用。最近的研究表明, Notch 信号通路的失调与重要肺部疾病的发病机制相关,特别是慢性阻塞性肺疾病(COPD)、肺纤维化、哮喘、肺动脉高压(PAH)、肺癌以及某些遗传性疾病中的肺部异常。在各种细胞和组织环境中,以及在生理和病理条件下, Notch 激活的多种后果已经被观察到。研究已经证实, Notch 信号级联与各种其他信号系统密切相关。本研究提供了 Notch 信号作用的最新概述,特别是其与纤维化的关系及其潜在的治疗意义。本研究揭示了关于异常或缺乏 Notch 活性在肺部疾病发生和发展中的机制和结果的最新发现。由于我们对这种信号机制的深入了解表明,调节 Notch 信号可能作为一种有价值的附加治疗方法,在未来的研究中具有潜力。

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