Department of Otolaryngology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
J Immunol Res. 2022 Jun 14;2022:2273121. doi: 10.1155/2022/2273121. eCollection 2022.
The pathogenesis of CRSwNP is complex and unclear. CRSwNP is subdivided into two types based on the infiltration of EOSs: eCRSwNP and noeCRSwNP. This study was designed to seek the role of autophagy, mitophagy, and Akt/mTOR pathway in these two subtypes of CRSwNP. This study included 29 patients with CRSwNP and 9 controls. The levels of autophagy, mitophagy, and Akt/mTOR pathway-related proteins in nasal tissues were quantified using western blot analysis. Levels of eosinophilic inflammation-related cytokines in nasal tissues were quantified by enzyme-linked immunosorbent assay. Immunohistochemistry was also used to evaluate autophagy, mitophagy, and Akt/mTOR pathway-related protein expression and distribution in nasal polyps and control tissues. Transmission electron microscopy was used to detect the formation of autophagosomes and mitochondrial autophagosomes. Masson's trichrome and periodic acid-Schiff Alcian blue staining were used to evaluate the severity of tissue remodeling. The expression of p-Akt/Akt and p-mTOR/mTOR was upregulated in patients with eCRSwNP or noeCRSwNP. Beclin 1, PINK1, BNIP3, and FUNDC1 levels were significantly reduced in the nasal polyps of patients with eCRSwNP or noeCRSwNP. Autophagosomes and mitochondrial autophagosomes formed less frequently in the nasal polyps of patients with eCRSwNP or noeCRSwNP. Levels of IL-4, IL-5, IL-13, and ECP and the eotaxins CCL11, CCL24, and CCL26 were elevated in the nasal polyps of patients with eCRSwNP or noeCRSwNP. Tissue remodeling is enhanced in patients with eCRSwNP or noeCRSwNP. The Akt/mTOR pathway, eosinophilic inflammation, and tissue remodeling are activated in the nasal polyps of patients with eCRSwNP or noeCRSwNP. The downregulation of autophagy and mitophagy is also observed in eosinophilic and noneosinophilic nasal polyps. The targeting of mitophagy may provide new therapeutic options for different endotypes of CRSwNP.
慢性鼻窦炎伴鼻息肉（CRSwNP）的发病机制复杂且尚不清楚。根据嗜酸性粒细胞（EOS）浸润情况，CRSwNP 可分为两种类型：嗜酸性粒细胞型 CRSwNP（eCRSwNP）和非嗜酸性粒细胞型 CRSwNP（noeCRSwNP）。本研究旨在探讨自噬、线粒体自噬和 Akt/mTOR 通路在这两种 CRSwNP 亚型中的作用。本研究纳入了 29 例 CRSwNP 患者和 9 例对照者。采用 Western blot 分析检测鼻组织中自噬、线粒体自噬和 Akt/mTOR 通路相关蛋白的水平。采用酶联免疫吸附试验检测鼻组织中嗜酸性粒细胞炎症相关细胞因子的水平。免疫组织化学法评估鼻息肉和对照组织中自噬、线粒体自噬和 Akt/mTOR 通路相关蛋白的表达和分布。透射电镜观察自噬体和线粒体自噬体的形成。Masson 三色和过碘酸-希夫阿尔辛蓝染色评估组织重塑的严重程度。eCRSwNP 或 noeCRSwNP 患者的 p-Akt/Akt 和 p-mTOR/mTOR 表达上调。eCRSwNP 或 noeCRSwNP 患者鼻息肉中 Beclin 1、PINK1、BNIP3 和 FUNDC1 的水平显著降低。eCRSwNP 或 noeCRSwNP 患者鼻息肉中自噬体和线粒体自噬体形成减少。eCRSwNP 或 noeCRSwNP 患者鼻息肉中白细胞介素 4（IL-4）、白细胞介素 5（IL-5）、白细胞介素 13（IL-13）和嗜酸性粒细胞阳离子蛋白（ECP）以及嗜酸性粒细胞趋化因子 CCL11、CCL24 和 CCL26 的水平升高。eCRSwNP 或 noeCRSwNP 患者的组织重塑增强。eCRSwNP 或 noeCRSwNP 患者鼻息肉中 Akt/mTOR 通路、嗜酸性粒细胞炎症和组织重塑被激活。在嗜酸性粒细胞型和非嗜酸性粒细胞型鼻息肉中也观察到自噬和线粒体自噬的下调。靶向线粒体自噬可能为 CRSwNP 的不同表型提供新的治疗选择。
