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

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.