title: Role of p19ink4d in the pathogenesis of hearing loss.
abstract: This study aimed to investigate the p19 expression in cisplatin-treated rats and the role of p19 in the degeneration of inner ear cells. It also searched for p19 gene alterations in patients with profound sensorineural deafness. P19ink4d is essential for the postmitotic maintenance of hair cells. It is presumed that a mutation in the functional homolog of p19 or a disturbance in its regulated expression can be the underlying cause of hearing loss. Experiments were conducted on male and female Sprague-Dawley rats (aged 6-7 weeks, 280-320 g) with thresholds of auditory brainstem responses <30 dB in the sound pressure level, and signs of middle ear infection were used for the experiment. For clinical evaluation, 400 children (age less than 13 years) from unrelated families with severe or profound sensorineural hearing loss (SNHL) were recruited at the second Xiangya Hospital of Central South University between 2005 and 2013, and genomic DNA for deafness gene analysis was obtained from peripheral blood samples of the patients and their lineal relatives. It was found that the p19 expression increased over time in the inner ear cells after cisplatin administration, but the p19 mRNA and protein levels significantly decreased in rats with manifested hearing loss induced by cisplatin. However, no mutation existed within the coding exons of p19 in the patients with profound sensorineural deafness. To conclude, the results support the concept that p19 may play an important role in the ototoxic effects of cisplatin and is probably involved in the pathogenesis of hearing loss.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital of Central South University Changsha, China.
authors.forename: Ruosha
authors.initials: R
authors.lastname: Lai
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital of Central South University Changsha, China.
authors.forename: Jingkun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital of Central South University Changsha, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Hu
authors.affiliation: Department of Pediatric Orthopedic, Hunan Provincial Peoples' Hospital Changsha, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital of Central South University Changsha, China ; Department of Otolaryngology, Miller School of Medicine, University of Miami Miami, Florida.
authors.forename: Qing
authors.initials: Q
authors.lastname: Jie
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital of Central South University Changsha, China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital of Central South University Changsha, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital of Central South University Changsha, China ; Department of Otolaryngology, Miller School of Medicine, University of Miami Miami, Florida.
authors.forename: Xuezhong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital of Central South University Changsha, China.
authors.forename: Dinghua
authors.initials: D
authors.lastname: Xie
mesh_terms: D000293:Adolescent; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D001489:Basilar Membrane / Q000378:metabolism / Q000473:pathology; D002648:Child; D002945:Cisplatin / Q000009:adverse effects*; D050764:Cyclin-Dependent Kinase Inhibitor p19 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism / Q000473:pathology; D034381:Hearing Loss / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017422:Sequence Analysis, DNA
chemical_list: C493974:CDKN2D protein, human; D050764:Cyclin-Dependent Kinase Inhibitor p19; D002945:Cisplatin
keywords: Inner ear cells; P19ink4d; hearing loss