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已发表论文
抑制 LOXL2 可减轻变应性鼻炎患者的鼻黏膜炎症和重塑
Authors Li Z, Wu G, Nie H, Li F, Wu Z, Wang F, Xie B
Received 17 April 2025
Accepted for publication 9 September 2025
Published 15 September 2025 Volume 2025:18 Pages 1283—1295
DOI https://doi.org/10.2147/JAA.S535065
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Luis Garcia-Marcos
Zhi Li,1 Geting Wu,2 Hui Nie,2 Feifeng Li,1 Zhen Wu,3 Fengjun Wang,4 Bin Xie2
1Department of Pathology, Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Pathology, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 3Department of Pathology, General Hospital of Hunan University of Medicine, Changsha, Hunan, People’s Republic of China; 4Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China
Correspondence: Bin Xie, Department of Pathology, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China, Email mrxiebin@163.com
Background: 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.
Methods: 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.
Results: 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-β 1, 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-β 1, α-SMA, and E-cadherin). In vitro, IL-4 stimulation significantly upregulated LOXL2, TGF-β 1, 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-β 1/Smad signaling pathway. In the AR mouse model, LOXL2 inhibitors significantly reduced nasal mucosal inflammation and tissue remodeling.
Conclusion: Our proteomic analysis suggests that LOXL2 may be involved in the pathological remodeling processes of AR, potentially through modulation of the TGF-β 1/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.
Keywords: allergic rhinitis, LOXL2, epithelial-mesenchymal transition, signaling pathway, tissue remodeling
1Department of Pathology, Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Pathology, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 3Department of Pathology, General Hospital of Hunan University of Medicine, Changsha, Hunan, People’s Republic of China; 4Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China
Correspondence: Bin Xie, Department of Pathology, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China, Email mrxiebin@163.com
Background: 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.
Methods: 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.
Results: 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-β 1, 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-β 1, α-SMA, and E-cadherin). In vitro, IL-4 stimulation significantly upregulated LOXL2, TGF-β 1, 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-β 1/Smad signaling pathway. In the AR mouse model, LOXL2 inhibitors significantly reduced nasal mucosal inflammation and tissue remodeling.
Conclusion: Our proteomic analysis suggests that LOXL2 may be involved in the pathological remodeling processes of AR, potentially through modulation of the TGF-β 1/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.
Keywords: allergic rhinitis, LOXL2, epithelial-mesenchymal transition, signaling pathway, tissue remodeling