Abstract：
Airway epithelial-mesenchymal transition (EMT) is the important pathological feature of airway remodeling in asthma. While macrolides are not commonly used to treat asthma, they have been shown to have protective effects on the airways, in which mechanisms are not yet fully understood. This study aims to investigate the impact of clarithromycin on airway EMT in asthma and its potential mechanism. The results revealed an increase in Kv1.3 expression in the airways of ovalbumin (OVA)-induced asthmatic mice, with symptoms and pathological changes being alleviated after treatment with the Kv1.3 inhibitor 5-(4-phenoxybutoxy)psoralen (PAP-1). Clarithromycin was found to attenuate airway epithelial-mesenchymal transition through the inhibition of Kv1.3 and PI3K/Akt signaling. Further experiments in vitro confirmed that PAP-1 could mitigate EMT by modulating the PI3K/Akt signaling in airway epithelial cells undergoing transformation into mesenchymal cells. These findings confirmed that clarithromycin might have a certain protective effect on asthma-related airway remodeling and represent a promising treatment strategy.
摘要：
气道上皮间质转化(EMT)是哮喘气道重塑的重要病理特征。虽然大环内酯类药物并不常用于治疗哮喘，它们已经被证明对气道有保护作用，其中机制尚未完全理解。本研究旨在探讨克拉霉素对哮喘气道EMT的影响及其可能的作用机制。结果显示，卵清蛋白（OVA）诱导的哮喘小鼠气道中Kv1.3表达增加，用Kv1.3抑制剂5-（4-苯氧氧基）补骨脂素（PAP-1）治疗后症状和病理变化得到缓解。发现克拉霉素通过抑制Kv1.3和PI3K/Akt信号传导减弱气道上皮-间质转化。进一步的体外实验证实，PAP-1可以通过调节气道上皮细胞转化为间充质细胞的PI3K/Akt信号传导来减轻EMT。这些发现证实，克拉霉素可能对哮喘相关的气道重塑具有一定的保护作用，并代表了一种有希望的治疗策略。
