Wnt activation protects against neomycin-induced hair cell damage in the cochlea.

Wnt activation protects against neomycin-induced hair cell damage in the mouse cochlea.:

Cell Death Dis. 2016;7:e2136

Authors: Liu L, Chen Y, Qi J, Zhang Y, He Y, Ni W, Li W, Zhang S, Sun S, Taketo MM, Wang L, Chai R, Li H

Abstract

Recent studies have reported the role of Wnt/β-catenin signaling in hair cell (HC) development, regeneration, and differentiation in the mouse cochlea; however, the role of Wnt/β-catenin signaling in HC protection remains unknown. In this study, we took advantage of transgenic mice to specifically knockout or overactivate the canonical Wnt signaling mediator β-catenin in HCs, which allowed us to investigate the role of Wnt/β-catenin signaling in protecting HCs against neomycin-induced damage. We first showed that loss of β-catenin in HCs made them more vulnerable to neomycin-induced injury, while constitutive activation of β-catenin in HCs reduced HC loss both in vivo and in vitro. We then showed that loss of β-catenin in HCs increased caspase-mediated apoptosis induced by neomycin injury, while β-catenin overexpression inhibited caspase-mediated apoptosis. Finally, we demonstrated that loss of β-catenin in HCs led to increased expression of forkhead box O3 transcription factor (Foxo3) and Bim along with decreased expression of antioxidant enzymes; thus, there were increased levels of reactive oxygen species (ROS) after neomycin treatment that might be responsible for the increased aminoglycoside sensitivity of HCs. In contrast, β-catenin overexpression reduced Foxo3 and Bim expression and ROS levels, suggesting that β-catenin is protective against neomycin-induced HC loss. Our findings demonstrate that Wnt/β-catenin signaling has an important role in protecting HCs against neomycin-induced HC loss and thus might be a new therapeutic target for the prevention of HC death.

PMID: 26962686 [PubMed – as supplied by publisher]

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1nCpsLt
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1QMjaEO
via IFTTT