Up-regulation of HIF1α in Refractory Sudden Sensorineural Hearing Loss| ACTA Otorhinolaryngologica Italica

Abstract

Objectives. To investigate expression of hypoxia-inducible Factor-1α (HIF-1a) in refractory sudden sensorineural hearing loss (SSNHL) patients. 

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

Results. Significant hearing improvement (≥15 dB) was observed in 16 patients [IMP GC sensitive (GCS) group], 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 expressions of HDAC2 and HIF-1a at post-IMP was significantly changed in the GCS group, but not in the GCR group. The same expression profile were also observed in HEI-OC1 cells exposed to oxidative stress (OS). The results of gene manipulation experiments indicate that HIF-1a up-regulation induced significantly HDAC2 reduced in HEI-OC1 cells, especially under OS condition.

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