title: Reduced expression of Connexin26 and its DNA promoter hypermethylation in the inner ear of mimetic aging rats induced by d-galactose.
abstract: Connexin26 (Cx26), one of the major protein subunits forming gap junctions (GJs), is important in maintaining homeostasis in the inner ear and normal hearing. Cx26 mutation is one of the most common causes for inherited nonsyndromic deafness, but the relationship between Cx26 and presbycusis is unknown. Our study aimed at exploring the expression and the aberrant methylation of the promoter region of Cx26 gene in the cochlea of inner ear mimetic aging rats. We applied a mimetic aging of inner ear rat model with mtDNA common deletion by d-gal injection for 8weeks. Real-time RT-PCR and Western blot of rat inner ear tissue indicated that the Cx26 expression decreased in the d-gal group. Further bisulfite sequencing analysis revealed that the methylation status of the promoter region of Cx26 gene in the d-gal group was higher than that in control group. These results indicated that the decrease of Cx26 expression might contribute to the development of presbycusis and the hypermethylation of promoter region of GJB2 might be associated with the Cx26 downregulation.
authors.affiliation: Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China. Electronic address: sunyu@hust.edu.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
authors.forename: Sen
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Otolaryngology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322-3030, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China; Institute of Otorhinolaryngology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China. Electronic address: entwjkong@hust.edu.cn.
authors.forename: Weijia
authors.initials: W
authors.lastname: Kong
mesh_terms: D000375:Aging / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D004272:DNA, Mitochondrial / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005690:Galactose / Q000008:administration & dosage; D017629:Gap Junctions / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D007279:Injections, Subcutaneous; D008969:Molecular Sequence Data; D011304:Presbycusis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D051381:Rats; D017208:Rats, Wistar; D017384:Sequence Deletion
chemical_list: D017630:Connexins; D004272:DNA, Mitochondrial; C000607044:Gjb2 protein, rat; D000072259:Connexin 26; D005690:Galactose
keywords: Aging; Common deletion; Connexin26; Hypermethylation; Presbycusis