The role and significance of YKL-40 in mucopathological remodeling in eosinophilic chronic rhinosinusitis.

OBJECTIVE: Medical and surgical treatments for eosinophilic chronic rhinosinusitis (ECRS) yield suboptimal efficacy, and the disease carries a high postoperative recurrence rate. Currently, there is a lack of histopathological and molecular markers for early identification of its characteristics. YKL-40, a chitinase-like protein, has been shown to be significantly elevated in ECRS patients and it is correlated with disease severity in previous studies. However, the role and mechanism of YKL-40 in promoting inflammation and tissue pathological changes in ECRS remain unclear. This study aimed to investigate the expression and correlation of YKL-40, TGF-β1, and fibrosis-related markers in ECRS patients and mouse models, and explore their regulatory mechanism in mucosal pathological remodeling, with unified diagnostic criteria for ECRS applied throughout. METHODS: An ECRS mouse model was established using ovalbumin (OVA) + Aspergillus protease (PA). ELISA, HE/Masson staining, immunohistochemistry, RT-qPCR, and Western Blot were used to detect inflammatory and remodeling-related indicators in mouse and human nasal mucosal tissues. Primary human ECRS nasal mucosal epithelial cells were isolated, and YKL-40 knockdown combined with TGF-β1 inhibitor intervention was performed to verify the regulatory relationship between YKL-40 and TGF-β1 signaling. RESULTS: ECRS with nasal polyps (ECRSwNP) patients showed higher preoperative and postoperative VAS scores, blood eosinophil indicators, and YKL-40 expression than non-ECRS patients. YKL-40 was positively correlated with disease severity, blood eosinophils, and submucosal collagen volume fraction (CVF) in ECRSwNP. The protein levels of TGF-β1, α-SMA, Collagen I, and Collagen III were significantly upregulated in ECRSwNP nasal polyps and positively correlated with YKL-40 expression. ECRS mice exhibited increased eosinophil infiltration, collagen deposition, and elevated levels of IL-4, IL-13, YKL-40, and TGF-β1. Antagonizing YKL-40 or TGF-β1 in mice attenuated Th2 inflammation, eosinophil infiltration, and collagen deposition. In primary ECRS epithelial cells, YKL-40 knockdown significantly downregulated TGF-β1, α-SMA, Collagen I, and Collagen III expression, with further inhibition observed after combined TGF-β1 blockade. CONCLUSIONS: YKL-40 is highly expressed in ECRS and positively correlated with disease severity and tissue fibrosis. YKL-40 synergizes with TGF-β1 to promote Th2-type inflammation and nasal mucosal pathological remodeling in ECRS. Targeted inhibition of the YKL-40/TGF-β1 axis alleviates mucosal inflammation and fibrosis, suggesting that YKL-40 may serve as a promising biomarker and therapeutic target for ECRS.