Wu Yujie, Zhu Xiaoyan, Gu Hongwei, Fu Feida, Guo Qinghua, Liu Ke, Yang Min, Zhang Tian, Wang Xu
Department of Otorhinolaryngology, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, 179 Xiaolingwei, Nanjing, 210014, Jiangsu, China.
Central Laboratory, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, China.
J Mol Histol. 2025 Aug 6;56(4):253. doi: 10.1007/s10735-025-10550-z.
Chronic rhinosinusitis (CRS) is a multifactorial inflammatory disease characterized by high prevalence and morbidity.Epithelial-to-mesenchymal transition (EMT) is associated with the pathophysiology of chronic rhinosinusitis with nasal polyp (CRSwNP).Since Neurotensin receptor 1 (NTSR1) signaling has been shown to regulate the EMT process in other diseases.In this study, we investigated the effect of NTSR1 on the EMT process in CRS, and explored whether these regulations could serve as potential drug targets.Our results demonstrated that NTS and NTSR1 expression was significantly elevated in CRS mice who were accompanied with mucosal thickening, goblet cell hyperplasia, glandular hyperplasia, and dense infiltration of inflammatory cells.Treatment with NTSR1 inhibitor SR48692 significantly improved the nasal symptoms and pathological conditions of sinus mucosa tissues in CRS mice.In addition, SR48692 treatment significantly downregulated the mRNA expression of Th2 cytokines (IL-4 and IL-5) and IL-17. Moreover, we observed that treatment with SR48692 significantly reduced the expression of a-SMA and vimentin, while increased that of E-cadherin, suggesting inhibition of EMT.Mechanistically, we further found that SR48692 could downregulate Wnt3a and β-catenin mRNA and protein levels impairing the Wnt/β-catenin pathway.Our results indicate that NTSR1 signaling promotes progression of EMT in mice with CRS may through Wnt3a/β-catenin pathway, underlining the promise of NTSR1 as a potential target for CRS therapy.
慢性鼻-鼻窦炎（CRS）是一种多因素炎症性疾病，具有高发病率和患病率。上皮-间质转化（EMT）与伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）的病理生理学相关。由于神经降压素受体1（NTSR1）信号通路已被证明在其他疾病中调节EMT过程。在本研究中，我们研究了NTSR1对CRS中EMT过程的影响，并探讨这些调节是否可作为潜在的药物靶点。我们的结果表明，NTS和NTSR1的表达在CRS小鼠中显著升高，伴有黏膜增厚、杯状细胞增生、腺体增生和炎性细胞密集浸润。用NTSR1抑制剂SR48692治疗可显著改善CRS小鼠的鼻部症状和鼻窦黏膜组织的病理状况。此外，SR48692治疗显著下调Th2细胞因子（IL-4和IL-5）和IL-17的mRNA表达。而且，我们观察到用SR48692治疗显著降低了α-SMA和波形蛋白的表达，同时增加了E-钙黏蛋白的表达，表示抑制了EMT。机制上，我们进一步发现SR48692可下调Wnt3a和β-连环蛋白的mRNA和蛋白水平，损害Wnt/β-连环蛋白通路。我们的结果表明，NTSR1信号通路可能通过Wnt3a/β-连环蛋白通路促进CRS小鼠EMT的进展，突出了NTSR1作为CRS治疗潜在靶点的前景。
