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Axonal Guidance Signaling Pathway Is Suppressed in Human Nasal Polyps

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机构: [1]Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts [2]Department of Otolaryngology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China [3]Department of Otolaryngology, University of Erlangen–Nuremberg, Erlangen, Germany [4]Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
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关键词: chronic rhinosinusitis nasal polyps proteome nerve axonal outgrowth innervation

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Background: Dysfunctional innervation might contribute to the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP), but the state of the axonal outgrowth signaling in CRSwNP is unknown. The purpose of this study was to explore the axonal outgrowth pathway-related protein expression in CRSwNP. Methods: Institutional review board approved study in which tissue proteomes were compared between control and CRSwNP patients (n = 10/group) using an aptamer-based proteomic array and confirmed by whole transcriptomic analysis. Results: Compared with controls, proteins associated with axonal guidance signaling pathway such as beta-nerve growth factor, semaphorin 3A, Ras-related C3 botulinum toxin substrate I, Bcl-2, protein kinase C delta type, and Fyn were significantly decreased in patients with CRSwNP (fold change [FC] 1.17, P = .002; FC = 1.09, P < .001; FC = -1.33, P < .001; FC 1.31, P < .001; FC = -1.31, P = .004; and FC = -1.20, P = 0.012, respectively). In contrast, reticulon-4 receptor, an inhibitory factor, was significantly increased in patients with CRSwNP (FC 1.25, P < .001). Furthermore, neuronal growth-associated proteins such as ciliary neurotrophic factor receptor subunit alpha, neuronal growth regulator I, neuronal cell adhesion molecule, neural cell adhesion molecule LI, platelet-derived growth factor subunit A, and netrin-4 were all significantly decreased in patients with CRSwNP (FC = -1.25, P < .001; FC = 1.27, P = .002; FC = -1.65, P = .013; FC = -4.20, P < .001; FC = -1.28, P < .001; and FC = -2.31, P < .001, respectively). In contrast, tissue eosinophil count (P < .001) and allergic inflammation factors such as IgE, periostin, and galectin-10 were all significantly increased in patients with CRSwNP (FC = 12.28, P <.001; FC 3.95, P < .001; and FC 2.44, P < .001, respectively). Furthermore, the log FC of the studied proteins expression significantly and positively correlated with log FC of their mRNA expression (P < .001, r = .88). Conclusions: Axonal guidance signaling and neural growth factors pathways proteins are significantly suppressed in eosinophilic CRSwNP.

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出版当年[2017]版:
大类 | 4 区 医学
小类 | 3 区 耳鼻喉科学
最新[2025]版:
大类 | 3 区 医学
小类 | 3 区 耳鼻喉科学
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出版当年[2016]版:
Q2 OTORHINOLARYNGOLOGY
最新[2024]版:
Q1 OTORHINOLARYNGOLOGY

影响因子: 最新[2024版] 最新五年平均 出版当年[2016版] 出版当年五年平均 出版前一年[2015版] 出版后一年[2017版]

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第一作者机构: [1]Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts [2]Department of Otolaryngology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China
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通讯机构: [1]Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts [*1]Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles Street, Boston, MA, USA.
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