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

Abstract

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