Deficit of mitogen-activated protein kinase phosphatase 1 (DUSP1) accelerates progressive hearing loss

Elife. 2019 Apr 2:8:e39159. doi: 10.7554/eLife.39159.

Abstract

Mitogen-activated protein kinases (MAPK) such as p38 and the c-Jun N-terminal kinases (JNKs) are activated during the cellular response to stress signals. Their activity is regulated by the MAPK-phosphatase 1 (DUSP1), a key component of the anti-inflammatory response. Stress kinases are well-described elements of the response to otic injury and the otoprotective potential of JNK inhibitors is being tested in clinical trials. By contrast, there are no studies exploring the role of DUSP1 in hearing and hearing loss. Here we show that Dusp1 expression is age-regulated in the mouse cochlea. Dusp1 gene knock-out caused premature progressive hearing loss, as confirmed by auditory evoked responses in Dusp1-/- mice. Hearing loss correlated with cell death in hair cells, degeneration of spiral neurons and increased macrophage infiltration. Dusp1-/- mouse cochleae showed imbalanced redox status and dysregulated expression of cytokines. These data suggest that DUSP1 is essential for cochlear homeostasis in the response to stress during ageing.

Keywords: apoptosis; cochlea; dual phosphatases; human biology; inflammation; medicine; mouse; neuroscience; oxidative stress; sensorineural hearing loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Cochlea / pathology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dual Specificity Phosphatase 1 / deficiency*
  • Evoked Potentials, Auditory
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Hair Cells, Auditory / pathology
  • Hearing Loss / physiopathology*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oxidation-Reduction

Substances

  • Cytokines
  • Dual Specificity Phosphatase 1
  • Dusp1 protein, mouse

Associated data

  • Dryad/10.5061/dryad.51m8c58