Bronchomotor tone imbalance evokes airway hyperresponsiveness.

Joseph A Jude, Reynold A Panettieri
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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.

支气管运动张力失衡会引起气道高反应性。
导言:气道阻塞性疾病哮喘和慢性阻塞性肺病给医疗保健带来了沉重负担。气道高反应性(AHR)是这两种疾病的显著特征,目前仍是主要的治疗目标。气道平滑肌(ASM)细胞对气道疾病中的支气管运动张力和气道高反应性的发展至关重要。ASM 细胞的收缩和松弛过程维持着支气管运动的平衡。了解破坏平衡的分子机制对确定 AHR 的新型治疗策略至关重要:根据文献综述和我们实验室已发表的研究结果,我们描述了内在和外在因素--疾病表型、毒物、炎症/重塑介质--这些因素放大了兴奋-收缩(E-C)耦合和 ASM 缩短,或减弱了松弛,从而改变了支气管运动平衡。我们认为,了解参与支气管运动张力失衡的 ASM 机制将为开发新型治疗方法提供平台,以治疗哮喘和慢性阻塞性肺疾病中的 AHR:ASM细胞的收缩和松弛过程受到内在和外在因素的调节,从而引起支气管运动张力失衡。创新的实验方法将成为阐明失衡机制和确定 AHR 新型治疗靶点的重要工具。
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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