Department of Medicine, Center for Translational Medicine and Division of Pulmonary, Allergy and Critical Care Medicine; and Jane & Leonard Korman Respiratory Institute, Thomas Jefferson University, Jefferson Alumni Hall, Room 543, 1020 Locust Street, Philadelphia, PA, 19107, USA.
Curr Allergy Asthma Rep. 2019 Sep 5;19(10):48. doi: 10.1007/s11882-019-0876-0.
Asthma is marked by peculiar pathological features involving airway contraction, an impinging inflammation in the lungs, and an inexorably progressive remodeling of pulmonary architecture. Current medications for management of asthma exacerbations fail to optimally mitigate these pathologies, which is partly due to the intrinsic heterogeneity in the development and progression of asthma within different populations. In recent years, the discovery of the ectopic expression of TAS2Rs in extraoral tissues and different cell types, combined with significant strides in gaining mechanistic understanding into receptor signaling and function, has revealed the potential to target TAS2Rs for asthma relief.
TAS2R activation leads to relaxation of airway smooth muscle cells and bronchodilation. In addition, findings from preclinical studies in murine model of asthma suggest that TAS2R agonists inhibit allergen-induced airway inflammation, remodeling, and hyperresponsiveness. In this review, we expand on the opportunity presented by TAS2Rs in the development of a comprehensive asthma treatment that overcomes the limitations set forth by current asthma therapeutics.
哮喘的特征为气道收缩、肺部炎症浸润和肺结构进行性不可逆转重塑等特殊病理特征。目前用于治疗哮喘急性发作的药物并不能很好地缓解这些病理变化，这在一定程度上是由于不同人群哮喘的发展和进展存在内在异质性。近年来，人们在口腔外组织和不同细胞类型中发现了 TAS2R 的异位表达，结合对受体信号和功能的机制理解取得的显著进展，为哮喘缓解的 TAS2R 靶向治疗提供了可能。
TAS2R 的激活可导致气道平滑肌松弛和支气管扩张。此外，哮喘小鼠模型的临床前研究结果表明，TAS2R 激动剂可抑制变应原诱导的气道炎症、重塑和高反应性。在这篇综述中，我们阐述了 TAS2R 在开发全面哮喘治疗中的机遇，该治疗方法克服了当前哮喘治疗方法的局限性。
