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瞬时受体电位阳离子通道亚家族 V(TRPV)及其在哮喘中的重要性。

Transient receptor potential cation channel subfamily V (TRPV) and its importance in asthma.

机构信息

Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, CDMX, México.

出版信息

Eur J Pharmacol. 2022 Jan 15;915:174692. doi: 10.1016/j.ejphar.2021.174692. Epub 2021 Dec 8.

DOI:10.1016/j.ejphar.2021.174692
PMID:34890545
Abstract

Transient receptor potential (TRP) ion channels play critical roles in physiological and pathological conditions. Increasing evidence has unveiled the contribution of TRP vanilloid (TRPV) family in the development of asthma. The TRPV family is a group (TRPV1-TRPV6) of polymodal channels capable of sensing thermal, acidic, mechanical stress, and osmotic stimuli. TRPVs can be activated by endogenous ligands including, arachidonic acid derivatives or endocannabinoids. While TRPV1-TRPV4 are non-selective cation channels showing a predominance for Ca over Na  influx, TRPV5 and TRPV6 are only Ca permeable selective channels. Asthma is a chronic inflammatory bronchopulmonary disorder involving airway hyperresponsiveness (AHR) and airway remodeling. Patients suffering from allergic asthma display an inflammatory pattern driven by cytokines produced in type-2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s). Ion channels are essential regulators in airway smooth muscle (ASM) and immune cells physiology. In this review, we summarize the contribution of TRPV1, TRPV2, and TRPV4 to the pathogenesis of asthma. TRPV1 is associated with hypersensitivity to environmental pollutants and chronic cough, inflammation, AHR, and remodeling. TRPV2 is increased in peripheral lymphocytes of asthmatic patients. TRPV4 contributes to ASM cells proliferation, and its blockade leads to a reduced eosinophilia, neutrophilia, as well as an abolished AHR. In conclusion, TRPV2 may represent a novel biomarker for asthma in children; meanwhile, TRPV1 and TRPV4 seem to be essential contributors to the development and exacerbations of asthma. Moreover, these channels may serve as novel therapeutic targets for this ailment.

摘要

瞬时受体电位 (TRP) 离子通道在生理和病理条件下发挥着关键作用。越来越多的证据揭示了 TRP 香草素 (TRPV) 家族在哮喘发展中的作用。TRPV 家族是一组(TRPV1-TRPV6)多模态通道,能够感知热、酸、机械应激和渗透刺激。TRPV 可以被内源性配体激活,包括花生四烯酸衍生物或内源性大麻素。虽然 TRPV1-TRPV4 是非选择性阳离子通道,对 Ca 内流的优先性大于 Na,但 TRPV5 和 TRPV6 仅为 Ca 通透选择性通道。哮喘是一种慢性炎症性支气管肺疾病,涉及气道高反应性 (AHR) 和气道重塑。过敏性哮喘患者表现出由 Th2 型辅助 T 细胞和 2 型先天淋巴样细胞 (ILC2) 产生的细胞因子驱动的炎症模式。离子通道是气道平滑肌 (ASM) 和免疫细胞生理学的重要调节剂。在这篇综述中,我们总结了 TRPV1、TRPV2 和 TRPV4 对哮喘发病机制的贡献。TRPV1 与对环境污染物的敏感性和慢性咳嗽、炎症、AHR 和重塑有关。哮喘患者外周淋巴细胞中 TRPV2 增加。TRPV4 有助于 ASM 细胞增殖,其阻断导致嗜酸性粒细胞、中性粒细胞减少以及 AHR 消失。总之,TRPV2 可能是儿童哮喘的新型生物标志物;同时,TRPV1 和 TRPV4 似乎是哮喘发展和恶化的重要贡献者。此外,这些通道可能成为该疾病的新治疗靶点。

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