Inhibition of LOXL2 Suppresses Nasal Mucosal Inflammation and Remodeling in Allergic Rhinitis

Tissue remodeling is a key feature of allergic rhinitis (AR), but its underlying molecular mechanisms remain unclear. Lysyl oxidase-like 2 (LOXL2), a regulator of tissue remodeling, has not been studied in AR. Proteomic analysis was performed on nasal mucosal tissues from 8 AR patients and 8 healthy controls (HCs) to identify differentially expressed proteins (DEPs). The top three upregulated DEPs and their association with tissue remodeling markers were validated by immunofluorescence, Western blot, and RT-qPCR in an independent cohort of 30 AR patients and 30 HCs. In vitro, human nasal epithelial cells (HNECs) were treated with IL-4, and the effects of candidate protein inhibitors on remodeling were assessed. An AR mouse model was used to evaluate the impact of these inhibitors on nasal inflammation and remodeling. Proteomic analysis revealed a disease-specific protein expression profile in the nasal mucosa of AR patients, with the top three upregulated proteins being LOXL2, TGF-β1, and TIRAP. Tissue validation showed that LOXL2 was significantly upregulated in the nasal mucosa of AR patients compared to HCs and was significantly correlated with EMT markers (TGF-β1, α-SMA, and E-cadherin). In vitro, IL-4 stimulation significantly upregulated LOXL2, TGF-β1, and α-SMA, while downregulating E-cadherin in a dose-dependent manner in human nasal epithelial cells. These effects were reversed by inhibition of LOXL2. Further investigations demonstrated that LOXL2 promotes tissue remodeling through activation of the TGF-β1/Smad signaling pathway. In the AR mouse model, LOXL2 inhibitors significantly reduced nasal mucosal inflammation and tissue remodeling. Our proteomic analysis suggests that LOXL2 may be involved in the pathological remodeling processes of AR, potentially through modulation of the TGF-β1/Smad signaling pathway. These findings provide preliminary evidence that LOXL2 could serve as a candidate biomarker and a possible therapeutic target in AR, warranting further investigation.