期刊
EXPERT OPINION ON THERAPEUTIC TARGETS
卷 27, 期 1, 页码 19-29出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14728222.2023.2177533
关键词
Lung; airway; airway smooth muscle; calcium; airway hyperreactivity; proliferation; fibrosis; drug targets
Asthma is characterized by enhanced airway contractility and remodeling, in which airway smooth muscle (ASM) plays a key role and is modulated by inflammation. Understanding the contribution of ASM to these features is crucial for the development of novel asthma therapies.
IntroductionAsthma is characterized by enhanced airway contractility and remodeling where airway smooth muscle (ASM) plays a key role, modulated by inflammation. Understanding the mechanisms by which ASM contributes to these features of asthma is essential for the development of novel asthma therapies.Areas coveredInflammation in asthma contributes to a multitude of changes within ASM including enhanced airway contractility, proliferation, and fibrosis. Altered intracellular calcium ([Ca2+](i)) regulation or Ca2+ sensitization contributes to airway hyperreactivity. Increased airway wall thickness from ASM proliferation and fibrosis contributes to structural changes seen with asthma.Expert opinionASM plays a significant role in multiple features of asthma. Increased ASM contractility contributes to hyperresponsiveness, while altered ASM proliferation and extracellular matrix production promote airway remodeling both influenced by inflammation of asthma and conversely even influencing the local inflammatory milieu. While standard therapies such as corticosteroids or biologics target inflammation, cytokines, or their receptors to alleviate asthma symptoms, these approaches do not address the underlying contribution of ASM to hyperresponsiveness and particularly remodeling. Therefore, novel therapies for asthma need to target abnormal contractility mechanisms in ASM and/or the contribution of ASM to remodeling, particularly in asthmatics resistant to current therapies.
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