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微小RNA-145-5p通过靶向鼻息肉慢性鼻窦炎中的CD40调节炎症反应。

MiR-145-5p Regulates Inflammatory Response via Targeting CD40 in Chronic Rhinosinusitis With Nasal Polyposis.

作者信息

Wang Lei, Wu Guangyao, Li Xixia, Liu Xiaoqin, Xu Xiaoyan

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, CR & WISCO General Hospital, Wuhan, China.

出版信息

APMIS. 2025 Jul;133(7):e70045. doi: 10.1111/apm.70045.

Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) lacks effective therapies, highlighting miRNAs as potential therapeutic targets owing to their biological functions and analytical accessibility. This study aimed to investigate the role of miR-145-5p in CRSwNP. Serum samples and inferior turbinate mucosa tissues were collected from 175 CRSwNP patients and 90 nasal septum deviation (NSD) subjects. qRT-PCR measured miR-145-5p expression in serum and tissue samples, and CD40 expression in tissues. ROC curve evaluated the diagnostic efficacy. Associations with disease severity and eosinophilic CRSwNP (ECRSwNP) risk were analyzed through correlation and logistic regression analysis. Dual-luciferase assay confirmed miR-145-5p targeting CD40. LPS-induced inflammation in human nasal epithelial cells (hNEpCs) assessed the miR-145-5p/CD40 axis's impact on IL-6, IL-1β, and TNF-α levels. Tissue and serum miR-145-5p effectively diagnosed CRSwNP. Reduced miR-145-5p correlated with disease severity and was an independent ECRSwNP risk factor. In LPS-stimulated hNEpCs, miR-145-5p overexpression suppressed IL-6, IL-1β, and TNF-α. CD40 expression inversely correlated with miR-145-5p and amplified inflammatory responses mitigated by miR-145-5p overexpression. MiR-145-5p, serving as a diagnostic biomarker for CRSwNP, was negatively correlated with disease severity. MiR-145-5p overexpression attenuated inflammation in hNEpCs by targeting CD40, thereby involving itself in the progression of CRSwNP, suggesting therapeutic potential for CRSwNP management.

摘要

伴有鼻息肉的慢性鼻-鼻窦炎(CRSwNP)缺乏有效的治疗方法,鉴于微小RNA(miRNA)的生物学功能及其分析的可及性,其有望成为潜在的治疗靶点。本研究旨在探究miR-145-5p在CRSwNP中的作用。收集了175例CRSwNP患者和90例鼻中隔偏曲(NSD)受试者的血清样本及下鼻甲黏膜组织。采用qRT-PCR检测血清和组织样本中miR-145-5p的表达以及组织中CD40的表达。通过ROC曲线评估诊断效能。通过相关性分析和逻辑回归分析疾病严重程度及嗜酸性粒细胞性CRSwNP(ECRSwNP)风险的相关性。双荧光素酶报告基因检测证实miR-145-5p靶向CD40。在人鼻上皮细胞(hNEpCs)中评估脂多糖(LPS)诱导的炎症反应,检测miR-145-5p/CD40轴对白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)水平的影响。组织和血清中的miR-145-5p可有效诊断CRSwNP。miR-145-5p表达降低与疾病严重程度相关,且是ECRSwNP的独立危险因素。在LPS刺激的hNEpCs中,miR-145-5p过表达可抑制IL-6、IL-1β和TNF-α。CD40表达与miR-145-5p呈负相关,且可放大miR-145-5p过表达减轻的炎症反应。miR-145-5p作为CRSwNP的诊断生物标志物,与疾病严重程度呈负相关。miR-145-5p过表达通过靶向CD40减轻hNEpCs中的炎症反应,从而参与CRSwNP的进展,提示其在CRSwNP治疗中的潜在价值。

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