Differences in the expression of multidrug resistance proteins in chronic rhinosinusitis according to endotype

鼻息肉 内型 医学 嗜酸性粒细胞 嗜酸性 鼻窦炎 免疫组织化学 免疫学 时间1 内科学 病理 基因表达 基因 生物 哮喘 生物化学
作者
Tomohisa Iinuma,Syuji Yonekura,Kiyoshi Hirahara,Junya Kurita,Riyo Yoneda,Toshiyasu Arai,Yuri Sonobe,Rie Shinmi,Yoshitaka Okamoto,Toyoyuki Hanazawa
出处
期刊:Allergology International [Elsevier]
卷期号:72 (4): 564-572
标识
DOI:10.1016/j.alit.2023.03.008
摘要

Chronic rhinosinusitis is a common disease of the nasal cavity and is classified into two major endotypes, which are neutrophilic and eosinophilic. Some patients with neutrophilic and eosinophilic chronic rhinosinusitis are refractory to treatment, and the mechanism of drug resistance is not completely understood.Nasal polyp samples were collected from patients with non-eosinophilic chronic rhinosinusitis (nECRS) and eosinophilic chronic rhinosinusitis (ECRS). Transcriptomic and proteomic analyses were performed simultaneously. Gene Ontology (GO) analysis was conducted to extract genes involved in drug resistance. Then, GO analysis results were validated via real-time polymerase chain reaction and immunohistochemistry analysis.The nasal polyps of patients with ECRS were enriched with 110 factors in the genes and 112 in the proteins, unlike in those of patients with nECRS. GO analysis on the combined results of both showed that the factors involved in extracellular transportation were enriched. Our analysis focused on multidrug resistance protein 1-5 (MRP1-5). Real-time polymerase chain reaction revealed that the MRP4 expression was significantly upregulated in ECRS polyps. Immunohistochemical staining showed that the MRP3 and MRP4 expressions significantly increased in nECRS and ECRS, respectively. MRP3 and MRP4 expressions were positively correlated with the number of neutrophil and eosinophil infiltrates in polyps and associated with the tendency to relapse in patients with ECRS.MRP is associated with treatment resistance and is expressed in nasal polyps. The expression pattern had different features based on chronic rhinosinusitis endotype. Therefore, drug resistance factors can be associated with therapeutic outcomes.
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