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.