Up-regulation of HIF-1α in refractory sudden sensorineural hearing loss.

IF 2.1 4区 医学 Q2 OTORHINOLARYNGOLOGY
Wandong She, Ziwen Gao, Wenyan Zhu, Mingfeng Guan, Jie Hou, Xiaorui Chen, Wei Ma
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引用次数: 0

Abstract

Objectives: To investigate the expression of hypoxia-inducible factor-1α (HIF-1α) in patients with refractory sudden sensorineural hearing loss (SSNHL).

Material and methods: Thirty patients with refractory SSNHL were treated with intratympanic methylprednisolone perfusion (IMP) for 10 days. Expression of HIF-1α and histone deacetylase 2 (HDAC2) was evaluated in peripheral blood mononuclear cells (PBMCs) and in vitro.

Results: Significant hearing improvement (≥ 15 dB) was observed in 16 patients [IMP glucocorticoid sensitive (GCS) group], while 14 patients had no therapeautic hearing recovery [IMP GC resistance (GCR) group]. The expression of HDAC2 decreased and HIF-1a increased in all refractory SSNHL patients before IMP. The expression of HDAC2 and HIF-1α after IMP was significantly changed in the GCS group, but not in the GCR group. The same expression profile was also observed in House Ear Institute-organ of Corti-1 (HEI-OC1) cells exposed to oxidative stress (OS). The results of gene manipulation experiments indicate that HIF-1α up-regulation significantly reduced HDAC2 expression in HEI-OC1 cells, especially under conditions of OS.

Conclusions: This study suggests that HIF-1α activation inhibits HDAC2 expression, causing glucocorticoid resistance in refractory SSNHL. HIF-1α might serve as a potential biomarker to predict prognosis of refractory SSNHL.

难治性突发性感音神经性听力损失中 HIF-1α 的上调。
研究目的研究难治性突发性感音神经性听力损失(SSNHL)患者体内缺氧诱导因子-1α(HIF-1α)的表达:30名难治性突发性感音神经性听力损失(SSNHL)患者接受了为期10天的鼓室内甲基强的松龙灌注(IMP)治疗。在外周血单核细胞(PBMCs)和体外对 HIF-1α 和组蛋白去乙酰化酶 2(HDAC2)的表达进行了评估:结果:16 例患者(IMP 糖皮质激素敏感(GCS)组)听力明显改善(≥ 15 dB),14 例患者(IMP GC 抵抗(GCR)组)听力无治疗性恢复。所有难治性 SSNHL 患者在接受 IMP 治疗前,HDAC2 的表达均下降,HIF-1a 的表达上升。IMP 后,GCS 组 HDAC2 和 HIF-1α 的表达发生了显著变化,而 GCR 组则没有。在暴露于氧化应激(OS)的House Ear Institute-organ of Corti-1(HEI-OC1)细胞中也观察到了相同的表达谱。基因操作实验结果表明,HIF-1α的上调显著降低了HDI-OC1细胞中HDAC2的表达,尤其是在OS条件下:本研究表明,HIF-1α的激活抑制了HDAC2的表达,从而导致难治性SSNHL对糖皮质激素产生耐药性。HIF-1α可作为预测难治性SSNHL预后的潜在生物标志物。
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来源期刊
Acta Otorhinolaryngologica Italica
Acta Otorhinolaryngologica Italica OTORHINOLARYNGOLOGY-
CiteScore
3.40
自引率
10.00%
发文量
97
审稿时长
6-12 weeks
期刊介绍: Acta Otorhinolaryngologica Italica first appeared as “Annali di Laringologia Otologia e Faringologia” and was founded in 1901 by Giulio Masini. It is the official publication of the Italian Hospital Otology Association (A.O.O.I.) and, since 1976, also of the Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale (S.I.O.Ch.C.-F.). The journal publishes original articles (clinical trials, cohort studies, case-control studies, cross-sectional surveys, and diagnostic test assessments) of interest in the field of otorhinolaryngology as well as clinical techniques and technology (a short report of unique or original methods for surgical techniques, medical management or new devices or technology), editorials (including editorial guests – special contribution) and letters to the Editor-in-Chief. Articles concerning science investigations and well prepared systematic reviews (including meta-analyses) on themes related to basic science, clinical otorhinolaryngology and head and neck surgery have high priority.
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