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miR-210 通过抑制低氧诱导因子(HIF)-1a 的表达来调节分泌性中耳炎的炎症反应。

miR-210 regulates the inflammation of otitis media with effusion by inhibiting the expression of hypoxia-inducible factor (HIF)-1a.

机构信息

Department of otorhinolaryngology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, Yiwu, 322000, PR China.

Department of otorhinolaryngology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, Yiwu, 322000, PR China.

出版信息

Biochem Biophys Res Commun. 2021 Jan 1;534:401-407. doi: 10.1016/j.bbrc.2020.11.068. Epub 2020 Nov 25.

DOI:10.1016/j.bbrc.2020.11.068
PMID:33248692
Abstract

Otitis media with effusion (OME) is the major cause of hearing impairment in children. miR-210 plays a critical role in inflammatory diseases, however, its role in OME is unknown. In this study, the miR-210 level in serum and middle ear effusion of is significantly down-regulated in serum, middle ear effusion from OME patients (100 cases) compared with healthy volunteers (50 cases). The expression of miR-210 is closely related to inflammatory factors and bone conduction disorder in patients with OME. In the in vitro study,the miR-210 level is significantly reduced in culture supernatant of lipopolysaccharide (LPS) treated human middle ear epithelial cells (HMEECs). miR-210 overexpression inhibited the LPS-induced in inflammatory cytokines production, cell viability reduction and cell apoptosis. Bioinformatics and dual-luciferase reporter assay showed that HIF-1a was a target gene of miR-210. The biological effects of miR-210 on cell viability, cell apoptosis and inflammation cytokines in LPS-induced HMEECs were reversed by HIF-1a overexpression. Furthermore, phosphorylation of NF-κB p65 was significantly decreased by miR-210 mediated HIF-1a in LPS-induced HMEECs. This study suggested that miR-210 may play a role in OME. Further studies are warranted to assess miR-210 as a potential target for the diagnosis and treatment of OME.

摘要

中耳积液(OME)是儿童听力障碍的主要原因。miR-210 在炎症性疾病中发挥着关键作用,但其在 OME 中的作用尚不清楚。在这项研究中,与健康志愿者(50 例)相比,OME 患者(100 例)血清和中耳积液中的 miR-210 水平明显下调。miR-210 的表达与 OME 患者的炎症因子和骨导障碍密切相关。在体外研究中,LPS 处理的人中耳上皮细胞(HMEEC)培养上清液中的 miR-210 水平显著降低。miR-210 过表达抑制 LPS 诱导的炎症细胞因子产生、细胞活力降低和细胞凋亡。生物信息学和双荧光素酶报告基因检测显示,HIF-1a 是 miR-210 的靶基因。HIF-1a 过表达逆转了 miR-210 对 LPS 诱导的 HMEECs 中细胞活力、细胞凋亡和炎症细胞因子的生物学效应。此外,miR-210 介导的 HIF-1a 显著降低了 LPS 诱导的 HMEECs 中 NF-κB p65 的磷酸化。本研究表明,miR-210 可能在 OME 中发挥作用。需要进一步研究评估 miR-210 作为 OME 诊断和治疗的潜在靶点。

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