Regulation of airway remodeling in asthma: The synergistic effects of nanotechnology and Hippo pathway activation

Asthma is a prevalent chronic respiratory condition characterized by airway remodeling, which contributes to irreversible airway narrowing and impaired lung function. Current therapies fail to effectively address this structural alteration. This study introduces an innovative strategy combining Quercetin, a natural flavonoid with anti-inflammatory and anti-proliferative properties, and chitosan-alginate nanoparticles (CA-NPs) to enhance bioavailability and therapeutic efficacy. By activating the Hippo signaling pathway, CA-NPs-Quercetin inhibits the proliferation and migration of human airway smooth muscle cells (HASMCs), key drivers of airway remodeling. In vitro experiments demonstrated significant suppression of HASMC proliferation and migration, with increased apoptosis rates attributed to the phosphorylation of YAP and TAZ, which restricted their nuclear translocation. In vivo experiments showed that CA-NPs-Quercetin significantly improved airway inflammation in asthmatic mice, reducing the total number of inflammatory cells and eosinophils in the bronchoalveolar lavage fluid, with a significant reduction in IL-4 expression (56.65%) and significant upregulation of IL-10 (130.91%) and IFN-γ (156.58%) levels. Moreover, CA-NPs-Quercetin reduced collagen deposition in lung tissue (Quercetin group reduced by 42.53% and CA-NPs-Quercetin group reduced by 73.20%) and improved lung function. This study provides a new approach for the application of Quercetin in asthma treatment and reveals the potential regulatory role of the Hippo pathway in asthma-related airway remodeling, demonstrating its broad application prospects in the treatment of respiratory diseases.