Role of p19ink4d in the pathogenesis of hearing loss

Int J Clin Exp Pathol. 2015 Oct 1;8(10):12243-51. eCollection 2015.


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.

Keywords: Inner ear cells; P19ink4d; hearing loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Auditory Threshold / drug effects
  • Basilar Membrane / metabolism
  • Basilar Membrane / pathology
  • Child
  • Cisplatin / adverse effects*
  • Cyclin-Dependent Kinase Inhibitor p19 / drug effects
  • Cyclin-Dependent Kinase Inhibitor p19 / genetics
  • Cyclin-Dependent Kinase Inhibitor p19 / metabolism*
  • Female
  • Hair Cells, Auditory, Inner / metabolism
  • Hair Cells, Auditory, Inner / pathology
  • Hearing Loss / chemically induced
  • Hearing Loss / metabolism
  • Hearing Loss / pathology*
  • Hearing Loss, Sensorineural / chemically induced
  • Hearing Loss, Sensorineural / metabolism
  • Hearing Loss, Sensorineural / pathology*
  • Humans
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Sequence Analysis, DNA


  • CDKN2D protein, human
  • Cyclin-Dependent Kinase Inhibitor p19
  • Cisplatin