2. Academic Validation
  3. Dibenzazepine promotes cochlear supporting cell proliferation and hair cell regeneration in neonatal mice

Dibenzazepine promotes cochlear supporting cell proliferation and hair cell regeneration in neonatal mice

  • Cell Prolif. 2020 Sep;53(9):e12872. doi: 10.1111/cpr.12872.
Jingfang Wu 1 2,  Xinran Dong 3,  Wen Li 1 2,  Liping Zhao 1 2,  Li Zhou 4,  Shan Sun 1 2,  Huawei Li 1 2 5
Affiliations

Affiliations

  • 1 Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
  • 2 NHC Key Laboratory of Hearing Medicine, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Biomedical Sciences, Fudan University School of Basic Medical Sciences, Shanghai, China.
  • 3 Molecular Medical Center, Children's Hospital of Fudan University, Shanghai, China.
  • 4 Shanghai High School, Shanghai, China.
  • 5 The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
PMID: 32677724 DOI: 10.1111/cpr.12872
Abstract

Objectives: To investigate the role of dibenzazepine (DBZ) in promoting supporting cell (SC) proliferation and hair cell (HC) regeneration in the inner ear.

Materials and methods: Postnatal day 1 wild-type or neomycin-damaged mouse cochleae were cultured with DBZ. Immunohistochemistry and scanning electron microscopy were used to examine the morphology of cochlear cells, and high-throughput RNA-sequencing was used to measure gene expression levels.

Results: We found that DBZ promoted SC proliferation and HC regeneration in a dose-dependent manner in both normal and damaged cochleae. In addition, most of the newly regenerated HCs induced by DBZ had visible and relatively mature stereocilia bundle structures. Finally, RNA sequencing detected the differentially expressed genes between DBZ treatment and controls, and interaction networks were constructed for the most highly differentially expressed genes.

Conclusions: Our study demonstrates that DBZ can significantly promote SC proliferation and increase the number of mitotically regenerated HCs with relatively mature stereocilia bundles in the neonatal mouse cochlea by inhibiting Notch signalling and activating Wnt signalling, suggesting the DBZ might be a new therapeutic target for stimulating HC regeneration.

Keywords

Notch signal; cell proliferation; cell regeneration; dibenzazepine; hair cells; supporting cells.

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