Cao Shouming, Niu Yan, Lou Wenrong, Wen Nannan, Chen Rui, Huang Haosu, Su Yuchao, Wu Haiying
Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
Department of Otolaryngology-Head and Neck Surgery, Yanan Hospital of Kunming Medical University, Kunming, People's Republic of China.
Am J Rhinol Allergy. 2025 Sep;39(5):353-363. doi: 10.1177/19458924251342999. Epub 2025 May 19.
BackgroundSquamous metaplasia is commonly observed in eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP). However, its underlying mechanisms remain unclear. This study aimed to evaluate the role of glucose transporter 1 (GLUT1) in the development of squamous metaplasia in eCRSwNP.MethodsTissue proteomics was employed to identify disease-specific proteins in eCRSwNP. Immunofluorescence, western blotting, and RT-qPCR were used for validation. Human nasal epithelial cells were utilized to assess GLUT1 expression and its regulatory mechanisms. A chronic rhinosinusitis with nasal polyps (CRSwNP) mouse model was used to examine the effect of GLUT1 inhibition on squamous metaplasia and nasal inflammation.ResultsProteomic analysis revealed a disease-specific protein expression profile in eCRSwNP polyps. Cohort validation demonstrated that GLUT1 and keratin 13 (KRT13) expression levels were significantly higher in the eCRSwNP group, with expression primarily localized in the epithelial regions. GLUT1 expression was positively correlated with the incidence of squamous metaplasia as well as KRT13 and involucrin (IVL) expression. In vitro experiments confirmed that combined Interleukin (IL)-4/IL-13 treatment upregulated GLUT1, KRT13, and IVL expression in human nasal epithelial cells in a dose-dependent manner, whereas GLUT1 inhibition reduced KRT13 and IVL expression, possibly through suppression of the PI3K-AKT signaling pathway. Animal experiments demonstrated that GLUT1 inhibition alleviated squamous metaplasia and inflammation in the nasal mucosa of mice.ConclusionElevated GLUT1 expression plays a key role in driving squamous metaplasia in eCRSwNP. GLUT1 inhibition attenuates nasal epithelial squamous metaplasia and inflammation in CRSwNP.
背景
在伴有鼻息肉的嗜酸性粒细胞性慢性鼻-鼻窦炎（eCRSwNP）中，鳞状化生较为常见。然而，其潜在机制尚不清楚。本研究旨在评估葡萄糖转运蛋白1（GLUT1）在eCRSwNP鳞状化生发展中的作用。
方法
采用组织蛋白质组学鉴定eCRSwNP中的疾病特异性蛋白质。通过免疫荧光、蛋白质印迹和逆转录-定量聚合酶链反应进行验证。利用人鼻上皮细胞评估GLUT1表达及其调控机制。使用伴有鼻息肉的慢性鼻-鼻窦炎（CRSwNP）小鼠模型，研究GLUT1抑制对鳞状化生和鼻炎症的影响。
结果
蛋白质组学分析揭示了eCRSwNP息肉中疾病特异性的蛋白质表达谱。队列验证表明，eCRSwNP组中GLUT1和角蛋白13（KRT13）的表达水平显著更高，表达主要定位于上皮区域。GLUT1表达与鳞状化生的发生率以及KRT13和内披蛋白（IVL）的表达呈正相关。体外实验证实，白细胞介素（IL）-4/IL-13联合处理以剂量依赖性方式上调人鼻上皮细胞中GLUT1、KRT13和IVL的表达，而GLUT1抑制则降低KRT13和IVL的表达，可能是通过抑制PI3K-AKT信号通路实现的。动物实验表明，GLUT1抑制可减轻小鼠鼻黏膜的鳞状化生和炎症。
结论
GLUT1表达升高在驱动eCRSwNP中的鳞状化生方面起关键作用。GLUT1抑制可减轻CRSwNP中鼻上皮的鳞状化生和炎症。
