UHRF1-induced connexin26 methylation is involved in hearing damage triggered by intermittent hypoxia in neonatal rats-Reference-Cited by-同舟云学术

UHRF1-induced connexin26 methylation is involved in hearing damage triggered by intermittent hypoxia in neonatal rats

Published:2023-01-01 Issue:1 Volume:18 Page:
ISSN:2391-5463
Container-title:Open Medicine
language:en
Short-container-title:

Author:

Zhang Xingang¹²,Zheng Jishan³,Xu Huiqing³,Ma Zhaoxin⁴

Affiliation:

1. Department of Otorhinolaryngology-Head and Neck Surgery, Shanghai East Hospital, Tongji University School of Medicine, Pudong New Area , Shanghai , 200120 , China

2. Department of Otorhinolaryngology-Head and Neck Surgery, Ningbo Women and Children’s Hospital , Ningbo , Zhejiang Province, 315012 , China

3. Department of Pediatrics, Ningbo Women and Children’s Hospital , Ningbo , Zhejiang Province, 315012 , China

4. Department of Otorhinolaryngology-Head and Neck Surgery, Tongji University School of Medicine , Pudong New Area, No. 150 Jimo Road , Shanghai , 200120 , China

Abstract

Abstract Ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) promotes the maintenance of established patterns of DNA methylation in mammalian cells. Extensive methylation of connexin26 (COX26) during hearing impairment has been demonstrated. The present study aims to determine whether UHRF1 can induce the methylation of COX26 in cochlea damaged by intermittent hypoxia (IH). After the establishment of the cochlear injury model through IH treatment or isolation of the cochlea containing Corti’s organ, pathological changes were observed via HE staining. Expressions of COX26 and UHRF1 were detected by quantitative reverse-transcription polymerase chain reaction and Western blot. The effect of COX26 methylation levels was analyzed by methylation-specific PCR (MSP). Phalloidin/immunofluorescence staining was used to observe structural changes. The binding relationship between UHRF1 and COX26 was verified by chromatin immunoprecipitation. IH caused cochlear damage, accompanied by increased methylation of COX26 and expression of UHRF1 in the cochlea of neonatal rats. CoCl2 treatment caused the loss of cochlear hair cells, downregulation and hypermethylation of COX26, abnormal upregulation of UHRF1, and disordered expressions of apoptosis-related proteins. UHRF1 in cochlear hair cells binds to COX26, and its knockdown upregulated COX26 level. Overexpressed COX26 partially alleviated the CoCl2-caused cell damage. UHRF1 induces COX26 methylation and aggravates the cochlear damage caused by IH.

Publisher

Walter de Gruyter GmbH

Subject

General Medicine

Link

https://www.degruyter.com/document/doi/10.1515/med-2023-0650/pdf

Reference35 articles.

1. Wroblewska-Seniuk KE, Dabrowski P, Szyfter W, Mazela J. Universal newborn hearing screening: methods and results, obstacles, and benefits. Pediatr Res. 2017;81(3):415–22.

2. Farinetti A, Raji A, Wu H, Wanna B, Vincent C. International consensus (ICON) on audiological assessment of hearing loss in children. Eur Ann Otorhinolaryngol Head Neck Dis. 2018;135(1s):S41–s8.

3. Park DJ, Ha S, Choi JS, Lee SH, Park JE, Seo YJ. Induced short-term hearing loss due to stimulation of age-related factors by intermittent hypoxia, high-fat diet, and galactose injection. Int J Mol Sci. 2020;21(19):7068.

4. Lieu JEC, Kenna M, Anne S, Davidson L. Hearing loss in children: A review. JAMA. 2020;324(21):2195–205.

5. Aronson JK, Ferner RE. Biomarkers – A general review. Curr Protoc Pharmacol. 2017;76:9.23.1–17.