PMID- 34091451
OWN - NLM
STAT- MEDLINE
DCOM- 20210805
LR  - 20210805
IS  - 1423-0275 (Electronic)
IS  - 0301-1569 (Print)
IS  - 0301-1569 (Linking)
VI  - 83
IP  - 4
DP  - 2021
TI  - Nuclear Factor Erythroid 2-Related Factor 2-Histone Deacetylase 2 Pathway in the 
      Pathogenesis of Refractory Sudden Sensorineural Hearing Loss and Glucocorticoid 
      Resistance.
PG  - 227-233
LID - 10.1159/000515205 [doi]
AB  - INTRODUCTION: A significant number of sensorineural hearing loss (SSNHL) patients 
      had no noticeable hearing improvement after glucocorticoid (GC) treatment. In the 
      present study, we examined expression of the nuclear factor erythroid 2-related 
      factor 2 (NRF2) and histone deacetylase 2 (HDAC2) in peripheral blood mononuclear 
      cells (PBMCs) of refractory SSNHL patients to study the role of NRF2-HDAC2 
      pathway in GC insensitivity hearing improvement after GC treatment, which is 
      usually referred to as refractory SSNHL or GC insensitivity. MATERIALS AND 
      METHODS: Forty-four refractory SSNHL patients were treated by intratympanic GC 
      infusion. Hearing was tested in all patients before and after treatment by pure 
      tone hearing test. NRF2/HDAC2 mRNA and protein levels were examined in PBMCs of 
      refractory SSNHL patients before and after treatment. PBMCs from healthy 
      volunteers were used as normal controls. RESULTS: According to the hearing 
      improvement after treatment, patients were assigned into 2 groups: the 
      intratympanic GC sensitive (IGCS) group (hearing recovery >/=15 dB HL) and the 
      intratympanic GC insensitive (IGCI) group (hearing recovery <15 dB HL). Before 
      treatment, the NRF2 mRNA level was lower in all patients than the normal control 
      group. After treatment, NRF2 and HDAC2 mRNA and protein levels were increased in 
      the IGCS group, while no significant change was observed in the IGCI group. 
      CONCLUSION: Low response of NRF2/HDAC2 proteins is associated with GC 
      insensitivity in SSNHL. We speculate that the NRF2-HDAC2 pathway affects GC 
      sensitivity in SSNHL patients.
CI  - The Author(s). Published by S. Karger AG, Basel.
FAU - Qi, Hui
AU  - Qi H
AD  - Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital, 
      the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
AD  - Department of Otorhinolaryngology, The Seventh Affiliated Hospital of Sun Yat-sen 
      University, Shenzhen, China.
FAU - Gao, Zi-Wen
AU  - Gao ZW
AD  - Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital 
      Clinical College of Nanjing Medical University, Nanjing, China.
FAU - Hou, Jie
AU  - Hou J
AD  - Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital, 
      the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
FAU - Zhou, Qiongqiong
AU  - Zhou Q
AD  - Department of Otolaryngology, Children's Hospital of Nanjing Medical University, 
      Nanjing, China.
FAU - Ma, Wei
AU  - Ma W
AD  - Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital 
      Clinical College of Nanjing Medical University, Nanjing, China.
FAU - Dai, Yan-Hong
AU  - Dai YH
AD  - Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital, 
      the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
AD  - Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital 
      Clinical College of Nanjing Medical University, Nanjing, China.
FAU - She, Wan-Dong
AU  - She WD
AD  - Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital, 
      the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
AD  - Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital 
      Clinical College of Nanjing Medical University, Nanjing, China.
LA  - eng
PT  - Journal Article
DEP - 20210604
PL  - Switzerland
TA  - ORL J Otorhinolaryngol Relat Spec
JT  - ORL; journal for oto-rhino-laryngology and its related specialties
JID - 0334721
RN  - 0 (Glucocorticoids)
RN  - 0 (NF-E2-Related Factor 2)
RN  - EC 3.5.1.98 (Histone Deacetylase 2)
SB  - IM
MH  - Audiometry, Pure-Tone
MH  - Glucocorticoids/therapeutic use
MH  - *Hearing Loss, Sensorineural/drug therapy
MH  - *Hearing Loss, Sudden
MH  - Histone Deacetylase 2/genetics
MH  - Humans
MH  - Leukocytes, Mononuclear
MH  - NF-E2-Related Factor 2/genetics
MH  - Treatment Outcome
PMC - PMC8315675
OTO - NOTNLM
OT  - Glucocorticoids
OT  - Hearing loss
OT  - Histone deacetylase 2
OT  - Nuclear factor erythroid 2-related factor 2
COIS- No conflict of interest relevant to this article was reported.
EDAT- 2021/06/07 06:00
MHDA- 2021/08/06 06:00
PMCR- 2021/06/04
CRDT- 2021/06/06 21:08
PHST- 2020/11/13 00:00 [received]
PHST- 2021/02/11 00:00 [accepted]
PHST- 2021/06/07 06:00 [pubmed]
PHST- 2021/08/06 06:00 [medline]
PHST- 2021/06/06 21:08 [entrez]
PHST- 2021/06/04 00:00 [pmc-release]
AID - 000515205 [pii]
AID - orl-0083-0227 [pii]
AID - 10.1159/000515205 [doi]
PST - ppublish
SO  - ORL J Otorhinolaryngol Relat Spec. 2021;83(4):227-233. doi: 10.1159/000515205. 
      Epub 2021 Jun 4.