G12/13 signaling in asthma.

IF 5.8 2区 医学 Q1 Medicine Respiratory Research Pub Date : 2024-08-02 DOI:10.1186/s12931-024-02920-0
Elizabeth L McDuffie, Reynold A Panettieri, Charles P Scott
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Abstract

Shortening of airway smooth muscle and bronchoconstriction are pathognomonic for asthma. Airway shortening occurs through calcium-dependent activation of myosin light chain kinase, and RhoA-dependent calcium sensitization, which inhibits myosin light chain phosphatase. The mechanism through which pro-contractile stimuli activate calcium sensitization is poorly understood. Our review of the literature suggests that pro-contractile G protein coupled receptors likely signal through G12/13 to activate RhoA and mediate calcium sensitization. This hypothesis is consistent with the effects of pro-contractile agonists on RhoA and Rho kinase activation, actin polymerization and myosin light chain phosphorylation. Recognizing the likely role of G12/13 signaling in the pathophysiology of asthma rationalizes the effects of pro-contractile stimuli on airway hyperresponsiveness, immune activation and airway remodeling, and suggests new approaches for asthma treatment.

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哮喘中的 G12/13 信号传导
气道平滑肌缩短和支气管收缩是哮喘的病理标志。气道缩短是通过钙依赖性激活肌球蛋白轻链激酶和 RhoA 依赖性钙敏化(抑制肌球蛋白轻链磷酸酶)发生的。人们对促收缩刺激激活钙敏化的机制还知之甚少。我们的文献综述表明,促收缩 G 蛋白偶联受体可能通过 G12/13 发出信号,激活 RhoA 并介导钙敏化。这一假设与原收缩激动剂对 RhoA 和 Rho 激酶活化、肌动蛋白聚合和肌球蛋白轻链磷酸化的影响相一致。认识到 G12/13 信号在哮喘病理生理学中可能扮演的角色,就能合理解释促收缩刺激对气道高反应性、免疫激活和气道重塑的影响,并为哮喘治疗提出新的方法。
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来源期刊
Respiratory Research
Respiratory Research RESPIRATORY SYSTEM-
CiteScore
9.70
自引率
1.70%
发文量
314
审稿时长
4-8 weeks
期刊介绍: Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.
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