siRNA targeting Hes5 augments hair cell regeneration in aminoglycoside-damaged mouse utricle

Mol Ther. 2013 Apr;21(4):834-41. doi: 10.1038/mt.2013.18. Epub 2013 Feb 26.


Notch signaling is active during the development of mosaic epithelial sheets and during their turnover and regeneration. After the loss of hair cells in the mosaic sheet of the vestibular sensory epithelium, new hair cells can be spontaneously generated by transdifferentiation of supporting cells. This regenerative process involves downregulation of the Hes5 gene and is known to be limited and incomplete, especially when the lesion is severe. Here, we test whether further downregulation of Hes5 gene accomplished by the use of siRNA after a severe lesion induced by an aminoglycoside in the mouse utricle can enhance the transdifferentiation of supporting cells and lead to the increased production of new hair cells. We demonstrate that Hes5 levels in the utricle decreased after the application of siRNA and that the number of hair cells in these utricles was significantly larger than following control treatment. The data suggest that siRNA technology may be useful for inducing repair and regeneration in the inner ear and that the Notch signaling pathway is a potentially useful target for specific gene expression inhibition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Female
  • Hair Cells, Auditory / cytology*
  • Hair Cells, Auditory / metabolism*
  • Mice
  • Myosin VIIa
  • Myosins / genetics
  • Myosins / metabolism
  • RNA, Small Interfering
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Saccule and Utricle / cytology*
  • Saccule and Utricle / metabolism*


  • Atoh1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Hes5 protein, mouse
  • Myo7a protein, mouse
  • Myosin VIIa
  • RNA, Small Interfering
  • Repressor Proteins
  • Myosins