The Roles of Autophagy, Mitophagy, and the Akt/mTOR Pathway in the Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps

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 wit...

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Main Authors: Chen Wang, Min-Li Zhou, Yong-Cai Liu, Ke-Jia Cheng
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2022/2273121
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author Chen Wang
Min-Li Zhou
Yong-Cai Liu
Ke-Jia Cheng
author_facet Chen Wang
Min-Li Zhou
Yong-Cai Liu
Ke-Jia Cheng
author_sort Chen Wang
collection DOAJ
description 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.
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spelling doaj-art-d5b92deee8614fa293fe3c8efaad3fb12025-02-03T01:23:10ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/2273121The Roles of Autophagy, Mitophagy, and the Akt/mTOR Pathway in the Pathogenesis of Chronic Rhinosinusitis with Nasal PolypsChen Wang0Min-Li Zhou1Yong-Cai Liu2Ke-Jia Cheng3Department of OtolaryngologyDepartment of OtolaryngologyDepartment of OtolaryngologyDepartment of OtolaryngologyThe 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.http://dx.doi.org/10.1155/2022/2273121
spellingShingle Chen Wang
Min-Li Zhou
Yong-Cai Liu
Ke-Jia Cheng
The Roles of Autophagy, Mitophagy, and the Akt/mTOR Pathway in the Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps
Journal of Immunology Research
title The Roles of Autophagy, Mitophagy, and the Akt/mTOR Pathway in the Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps
title_full The Roles of Autophagy, Mitophagy, and the Akt/mTOR Pathway in the Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps
title_fullStr The Roles of Autophagy, Mitophagy, and the Akt/mTOR Pathway in the Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps
title_full_unstemmed The Roles of Autophagy, Mitophagy, and the Akt/mTOR Pathway in the Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps
title_short The Roles of Autophagy, Mitophagy, and the Akt/mTOR Pathway in the Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps
title_sort roles of autophagy mitophagy and the akt mtor pathway in the pathogenesis of chronic rhinosinusitis with nasal polyps
url http://dx.doi.org/10.1155/2022/2273121
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