气道上皮—间充质转化在哮喘气道重塑中的作用研究进展

Research progress on the role of airway epithelial-mesenchymal transition in airway remodeling in asthma

摘要

支气管哮喘是以慢性气道炎症、可逆性气流受限以及气道重塑为核心特征的异质性疾病，气道重塑是病情进展为重度、难治性哮喘的关键病理基础。上皮-间充质转化（epithelial-mesenchymal transition，EMT）作为气道重塑的早期核心事件与首要特征，由过敏原、PM2.5、烟草烟雾等有害刺激直接损伤气道上皮屏障启动，并在转化生长因子（transformation growth factor，TGF）-β、白细胞介素家族、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）等炎症因子及PI3K/AKT、Smad、Wnt/β-catenin等信号通路共同调控下发生，伴随E-cadherin表达下降，α-SMA及波形蛋白等间质标志物升高。miRNA、lncRNA等非编码RNAs及 PER2、 GLCCI1等关键基因在转录与表观层面参与EMT精细调控。目前生物制剂、大环内酯类、激素、信号通路抑制剂及中医药等均显示出抑制EMT、改善气道重塑的潜力，但临床转化仍面临生理功能干扰、表型异质性、长期安全性不明及缺乏大样本临床证据等挑战。深入阐明哮喘气道重塑中EMT的调控网络，探索精准、可逆、安全的靶向干预策略，对逆转气道重塑、改善重症与难治性哮喘预后具有重要理论价值与临床意义。

Abstract

Bronchial asthma is a heterogeneous disease characterized by chronic airway inflammation, reversible airflow limitation and airway remodeling. Airway remodeling is the key pathological basis for the progression of mild asthma to severe and refractory asthma. As an early core event and primary feature of airway remodeling, epithelial-mesenchymal transition (EMT) is initiated by direct damage to the airway epithelial barrier caused by harmful stimuli such as allergens, PM2.5 and tobacco smoke. It is coordinately regulated by inflammatory factors including TGF-β, the interleukin family, TNF-α and signaling pathways such as PI3K/AKT, Smad and Wnt/β-catenin, accompanied by downregulated expression of E-cadherin and elevated levels of mesenchymal markers including α-SMA and vimentin. Non-coding RNAs (miRNA, lncRNA) and key genes such as PER2 and GLCCI1 participate in the fine regulation of EMT at the transcriptional and epigenetic levels. At present, biologics, macrolides, hormones, signaling pathway inhibitors and traditional Chinese medicine have shown potential in inhibiting EMT and improving airway remodeling. However, clinical translation still faces challenges including disturbance of physiological functions, phenotypic heterogeneity, unclear long-term safety and insufficient large-sample clinical evidence. Further elucidation of the regulatory network of EMT in asthma airway remodeling and exploration of precise, reversible and safe targeted intervention strategies are of great theoretical value and clinical significance for reversing airway remodeling and ameliorating the prognosis of severe and refractory asthma.

关键词

支气管哮喘 / 上皮细胞 / 上皮-间充质转化 / 气道上皮屏障 / 气道重塑 / 信号通路 / 难治性哮喘 / 非编码RNAs

Key words

bronchial asthma / epithelial cells / epithelial-mesenchymal transition / airway epithelial barrier / airway remodeling / signaling pathways / refractory asthma / non-coding RNAs

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基金资助

广西自然科学基金资助项目(2025GXNSFAA069766)