Li Lifei, Zhang Wei, Qiu Chen
Department of Respiratory and Critical Care Medicine, Institute of Shenzhen Respiratory Diseases, The First Affiliated Hospital (Shenzhen People's Hospital), School of Medicine, Southern University of Science and Technology, Shenzhen, China.
Ann Transl Med. 2022 Aug;10(15):838. doi: 10.21037/atm-22-3219.
Airway remodeling in asthma refers to numerous structural changes in the airway in asthmatic patients, with thickening of the airway smooth muscle layer as its core feature. However, the nature and sources of the abnormally increased airway smooth muscle cells (ASMCs) in airway remodeling remain unclear. ASMCs play a key role in the pathogenesis of fatal asthma; therefore, it is important to clarify the properties and sources of these ASMCs responsible for asthmatic airway remodeling, which may provide a new direction for the precise treatment for asthma.
We performed a narrative review of the literature on PubMed, Web of Science, and Google Scholar databases searching for the cellular sources of ASMCs in asthmatic airway remodeling and their clinical relevance.
It has long been thought that ASMCs are the result of abnormal proliferation of the native ASMCs in asthma; however, increasing evidence suggests that increased "ASMCs" may be due to the differentiation/transdifferentiation of other cells including mesenchymal stem cells (MSCs), myofibroblasts (MYFs), pericytes, and epithelial-mesenchymal transition (EMT). Recently, several pharmacological and biological therapies aimed at "reducing asthmatic ASMCs" have been developed, among which gallopamil, JQ1 [an inhibitor of the bromodomain and extra-terminal domain (BET) protein family], and histone deacetylase (HDAC) inhibitors can alleviate asthma airway remodeling and hyperresponsiveness and improve asthma symptoms in both mouse models and preclinical experiments.
As one of the core features of asthma, ASMCs are an important effector of airway remodeling. It has become extremely important to develop therapies for the reduction and prevention of the "ASMCs" on the basis of the properties and sources of "ASMCs". Many studies have shown that epigenetic regulation is closely related to the abnormal increase of ASMCs in asthma, and interfering with epigenetic regulation factors can reduce the increased smooth muscle cells. Although the epigenetic regulation of asthma is still in its nascent stage, epigenetic therapy targeting "ASMCs" may become another new strategy for asthma prevention and treatment.
哮喘中的气道重塑是指哮喘患者气道发生的众多结构变化，气道平滑肌层增厚是其核心特征。然而，气道重塑过程中气道平滑肌细胞（ASMCs）异常增多的性质和来源仍不清楚。ASMCs在致死性哮喘的发病机制中起关键作用；因此，明确这些导致哮喘气道重塑的ASMCs的特性和来源很重要，这可能为哮喘的精准治疗提供新方向。
我们对PubMed、科学网和谷歌学术数据库中有关哮喘气道重塑中ASMCs的细胞来源及其临床相关性的文献进行了叙述性综述。
长期以来人们一直认为ASMCs是哮喘中天然ASMCs异常增殖的结果；然而，越来越多的证据表明，增多的“ASMCs”可能是由于包括间充质干细胞（MSCs）、肌成纤维细胞（MYFs）、周细胞以及上皮-间质转化（EMT）在内的其他细胞的分化/转分化所致。最近，已开发出几种旨在“减少哮喘ASMCs”的药物和生物疗法，其中维拉帕米、JQ1[一种溴结构域和额外末端结构域（BET）蛋白家族抑制剂]以及组蛋白去乙酰化酶（HDAC）抑制剂在小鼠模型和临床前实验中均可减轻哮喘气道重塑和高反应性并改善哮喘症状。
作为哮喘的核心特征之一，ASMCs是气道重塑的重要效应细胞。基于“ASMCs”的特性和来源开发减少和预防“ASMCs”的疗法变得极为重要。许多研究表明，表观遗传调控与哮喘中ASMCs的异常增多密切相关，干扰表观遗传调控因子可减少增多的平滑肌细胞。尽管哮喘的表观遗传调控仍处于起步阶段，但针对“ASMCs”的表观遗传疗法可能成为哮喘防治的另一种新策略。
