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气道平滑肌张力失衡可诱发气道高反应性。

Bronchomotor tone imbalance evokes airway hyperresponsiveness.

机构信息

Rutgers Institute for Translational Medicine and Science, Child Health Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.

出版信息

Expert Rev Respir Med. 2024 Nov;18(11):835-841. doi: 10.1080/17476348.2024.2419543. Epub 2024 Oct 23.

DOI:10.1080/17476348.2024.2419543
PMID:39435484
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11580617/
Abstract

INTRODUCTION

Obstructive airway diseases asthma and COPD represent a significant healthcare burden. Airway hyperresponsiveness (AHR), a salient feature of these two diseases, remains the main therapeutic target. Airway smooth muscle (ASM) cell is pivotal for bronchomotor tone and development of AHR in airway diseases. The contractile and relaxation processes in ASM cells maintain a homeostatic bronchomotor tone. It is critical to understand the molecular mechanisms that disrupt the homeostasis to identify novel therapeutic strategies for AHR.

AREAS COVERED

Based on review of literature and published findings from our laboratory, we describe intrinsic and extrinsic factors - disease phenotype, toxicants, inflammatory/remodeling mediators- that amplify excitation-contraction (E-C) coupling and ASM shortening and or diminish relaxation to alter bronchomotor homeostasis. We posit that an understanding of the ASM mechanisms involved in bronchomotor tone imbalance will provide platforms to develop novel therapeutic approaches to treat AHR in asthma and COPD.

EXPERT OPINION

Contractile and relaxation processes in ASM cell are modulated by intrinsic and extrinsic factors to elicit bronchomotor tone imbalance. Innovative experimental approaches will serve as essential tools for elucidating the imbalance mechanisms and to identify novel therapeutic targets for AHR.

摘要

简介

阻塞性气道疾病哮喘和 COPD 给医疗保健带来了巨大负担。气道高反应性(AHR)是这两种疾病的显著特征,仍然是主要的治疗靶点。气道平滑肌(ASM)细胞对于支气管运动张力和气道疾病中 AHR 的发展至关重要。ASM 细胞的收缩和松弛过程维持着支气管运动张力的内稳态。了解破坏内稳态的分子机制对于确定 AHR 的新治疗策略至关重要。

涵盖领域

基于文献综述和我们实验室发表的研究结果,我们描述了内在和外在因素——疾病表型、毒素、炎症/重塑介质——这些因素放大兴奋-收缩(E-C)偶联和 ASM 缩短,并或减少松弛,从而改变支气管运动的内稳态。我们假设,对参与支气管运动张力失衡的 ASM 机制的理解将为开发治疗哮喘和 COPD 中 AHR 的新治疗方法提供平台。

专家意见

ASM 细胞的收缩和松弛过程受内在和外在因素的调节,从而引起支气管运动张力失衡。创新的实验方法将作为阐明失衡机制和确定 AHR 新治疗靶点的重要工具。

相似文献

1
Bronchomotor tone imbalance evokes airway hyperresponsiveness.气道平滑肌张力失衡可诱发气道高反应性。
Expert Rev Respir Med. 2024 Nov;18(11):835-841. doi: 10.1080/17476348.2024.2419543. Epub 2024 Oct 23.
2
Molecular mechanisms underlying airway smooth muscle contraction and proliferation: implications for asthma.气道平滑肌收缩与增殖的分子机制:对哮喘的影响
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Minerva Med. 2022 Feb;113(1):4-16. doi: 10.23736/S0026-4806.21.07283-9. Epub 2021 Jan 26.
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Am J Respir Cell Mol Biol. 2018 May;58(5):575-584. doi: 10.1165/rcmb.2017-0247OC.
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Models to understand contractile function in the airways.用于理解气道收缩功能的模型。
Pulm Pharmacol Ther. 2011 Oct;24(5):444-51. doi: 10.1016/j.pupt.2011.04.028. Epub 2011 Apr 14.
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[Molecular mechanisms of the hyperresponsiveness of airway smooth muscle in bronchial asthma].[支气管哮喘气道平滑肌高反应性的分子机制]
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Airway smooth muscle as a regulator of immune responses and bronchomotor tone.气道平滑肌作为免疫反应和支气管运动张力的调节因子。
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Attenuation of relaxing response induced by pituitary adenylate cyclase-activating polypeptide in bronchial smooth muscle of experimental asthma.实验性哮喘支气管平滑肌中垂体腺苷酸环化酶激活肽诱导松弛反应的衰减。
Am J Physiol Lung Cell Mol Physiol. 2020 Nov 1;319(5):L786-L793. doi: 10.1152/ajplung.00315.2020. Epub 2020 Sep 2.

本文引用的文献

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Airway hyperresponsiveness in asthma: The role of the epithelium.哮喘中的气道高反应性:上皮细胞的作用。
J Allergy Clin Immunol. 2024 May;153(5):1181-1193. doi: 10.1016/j.jaci.2024.02.011. Epub 2024 Feb 21.
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Rho-Kinase Inhibition of Active Force and Passive Tension in Airway Smooth Muscle: A Strategy for Treating Airway Hyperresponsiveness in Asthma.Rho激酶对气道平滑肌主动力和被动张力的抑制作用:一种治疗哮喘气道高反应性的策略。
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Rhinovirus C15 Attenuates Relaxation and cAMP Production in Human Airways and Smooth Muscle.
鼻病毒 C15 减弱人气道和平滑肌的舒张和 cAMP 产生。
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Starving a Cell Promotes Airway Smooth Muscle Relaxation: Inhibition of Glycolysis Attenuates Excitation-Contraction Coupling.细胞饥饿促进气道平滑肌松弛:糖酵解抑制减弱兴奋-收缩耦联。
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Obesity elicits a unique metabolomic signature in human airway smooth muscle cells.肥胖会在人类气道平滑肌细胞中引起独特的代谢组学特征。
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Inhibition of ABCC1 Decreases cAMP Egress and Promotes Human Airway Smooth Muscle Cell Relaxation.ABCC1 抑制减少 cAMP 外排并促进人呼吸道平滑肌细胞松弛。
Am J Respir Cell Mol Biol. 2022 Jan;66(1):96-106. doi: 10.1165/rcmb.2021-0345OC.
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FFAR1 activation attenuates histamine-induced myosin light chain phosphorylation and cortical tension development in human airway smooth muscle cells.FFAR1 激活可减轻人呼吸道平滑肌细胞中组胺诱导的肌球蛋白轻链磷酸化和皮质张力发展。
Respir Res. 2020 Nov 30;21(1):317. doi: 10.1186/s12931-020-01584-w.
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Rhinovirus C15 Induces Airway Hyperresponsiveness via Calcium Mobilization in Airway Smooth Muscle.鼻病毒 C15 通过气道平滑肌内钙离子动员诱导气道高反应性。
Am J Respir Cell Mol Biol. 2020 Mar;62(3):310-318. doi: 10.1165/rcmb.2019-0004OC.
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Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children.转录组网络鉴定儿童病毒和非病毒哮喘恶化的机制。
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