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PI3K信号通路在哮喘气道炎症和重塑中的机制及治疗意义

The Mechanisms and Therapeutic Implications of PI3K Signaling in Airway Inflammation and Remodeling in Asthma.

作者信息

Song Bangguo, Hu Jihong, Chen Shupeng, Zhang Yang

机构信息

School of Clinical Chinese Medicine, Gansu University of Traditional Chinese Medicine, Gansu, People's Republic of China.

Teaching Experimental Training Center, Gansu University of Traditional Chinese Medicine, Gansu, People's Republic of China.

出版信息

Biologics. 2025 Mar 7;19:73-86. doi: 10.2147/BTT.S497622. eCollection 2025.

Abstract

Bronchial asthma is a complex and heterogeneous disease with ongoing airway inflammation and increased airway responsiveness. Key characteristics of the disease include persistent airway inflammation, airway hyperresponsiveness, and airway remodeling. Asthma's chronic and recurrent characteristics contribute to airway remodeling and inflammation, which can exacerbate lung damage. Presently, inflammation is predominantly managed with corticosteroids, yet there is a notable absence of treatments specifically addressing airway remodeling. The phosphoinositide 3-kinase (PI3K) signaling pathway is integral to the processes of inflammation, airway remodeling, and immune responses. Pharmacological agents targeting this pathway are currently undergoing clinical evaluation. This review elucidates the role of PI3K in the immune responses, airway inflammation, and remodeling associated with asthma, examining its underlying mechanisms. Furthermore, we synthesize the existing literature on the therapeutic potential of PI3K inhibitors for asthma management, emphasizing immune modulation, airway inflammation, and remodeling, including drug development and ongoing clinical trials. Lastly, we explore how various PI3K-targeted therapies may enhance efficacy and improve tolerance.

摘要

支气管哮喘是一种复杂的异质性疾病,伴有持续的气道炎症和气道反应性增加。该疾病的关键特征包括持续性气道炎症、气道高反应性和气道重塑。哮喘的慢性和复发性特征会导致气道重塑和炎症,进而加重肺损伤。目前,炎症主要通过皮质类固醇进行控制,但明显缺乏专门针对气道重塑的治疗方法。磷酸肌醇3-激酶(PI3K)信号通路在炎症、气道重塑和免疫反应过程中不可或缺。目前,针对该通路的药物正在进行临床评估。这篇综述阐明了PI3K在与哮喘相关的免疫反应、气道炎症和重塑中的作用,并探讨了其潜在机制。此外,我们综合了现有关于PI3K抑制剂在哮喘治疗中的潜在作用的文献,重点关注免疫调节、气道炎症和重塑,包括药物研发和正在进行的临床试验。最后,我们探讨了各种针对PI3K的治疗方法如何提高疗效和改善耐受性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c19a/11895685/a9d9280e5fe6/BTT-19-73-g0001.jpg

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