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Fucoidan promotes mechanosensory hair cell regeneration following amino glycoside-induced cell death

Authors
 In Seok Moon ; Ju-Hoon So ; Jae Young Choi ; Cheol-Hee Kim ; Jung-Hwa Choi ; Eun Young Kim ; Won-Sang Lee ; Young-Mi Jung 
Citation
 Hearing Research, Vol.282(1-2) : 236~242, 2011 
Journal Title
 Hearing Research 
ISSN
 0378-5955 
Issue Date
2011
Abstract
OBJECTIVE: Lateral line system of the zebrafish is a useful model for study of hair cell toxicity and regeneration. We found that low molecular weight fucoidan (LMWF) stimulated the regeneration of mechanosensory hair cells after neomycin-induced cell death in zebrafish lateral line. The aims of this study were to quantify the regenerative effects of LMWF and determine their relationship to the Notch and FGF signaling pathways. METHODS: Wild-type zebrafish and three different transgenic zebrafish lines (Pou4f3::GFP, scm1::GFP, and ET20::GFP) were used. At 4.5-6 days post-fertilization, lateral line hair cells of larvae were eliminated using neomycin (500 μM). Larvae were then treated with LMWF. Neuromasts were observed using confocal microscopy. Stereocilia morphology was observed using scanning electron microscopy, and the location and status of regeneration was assessed using 5-bromo-2-deoxyuridine (BrdU) incorporation. RESULTS: Hair cells damaged by neomycin treatment regenerated faster in wild-type and Pou4f3::GFP larvae treated with LMWF (50 μg/ml) than in untreated controls. LMWF also enhanced the regeneration of supporting cells in scm1::GFP and ET20::GFP larvae. Increased numbers of BrdU-labeled cells were found after LMWF treatment in neuromast regions corresponding to internal and peripheral supporting cells. The effect of LMWF was mimicked by the Notch signaling inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT), but the effects of LMWF and DAPT were not additive. CONCLUSION: LMWF enhances the regeneration of hair cells damaged by neomycin. The mechanism may involve the Notch signaling pathway. LMWF shows promise as a therapeutic agent for hearing and balance disorders.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/95074
DOI
10.1016/j.heares.2011.07.007
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Medical Research Center
1. 연구논문 > 1. College of Medicine > Dept. of Otorhinolaryngology
Yonsei Authors
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Link
 http://www.sciencedirect.com/science/article/pii/S0378595511001985
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