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

 In Seok Moon  ;  Ju-Hoon So  ;  Young-Mi Jung  ;  Won-Sang Lee  ;  Eun Young Kim  ;  Jung-Hwa Choi  ;  Cheol-Hee Kim  ;  Jae Young Choi 
 HEARING RESEARCH, Vol.282(1-2) : 236-242, 2011 
Journal Title
Issue Date
Aminoglycosides/toxicity* ; Animals ; Animals, Genetically Modified ; Cell Death/drug effects ; Cell Proliferation/drug effects* ; Dose-Response Relationship, Drug ; Fibroblast Growth Factors/metabolism ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Hair Cells, Auditory/drug effects* ; Hair Cells, Auditory/metabolism ; Hair Cells, Auditory/ultrastructure ; Labyrinth Supporting Cells/drug effects ; Labyrinth Supporting Cells/pathology ; Lateral Line System/drug effects* ; Lateral Line System/metabolism ; Lateral Line System/ultrastructure ; Mechanotransduction, Cellular/drug effects* ; Microscopy, Confocal ; Microscopy, Electron, Scanning ; Neomycin/toxicity* ; Polysaccharides/pharmacology* ; Receptors, Notch/metabolism ; Regeneration/drug effects* ; Time Factors ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Zebrafish/embryology
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.
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1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Moon, In Seok(문인석) ORCID logo https://orcid.org/0000-0002-3951-5074
Lee, Won Sang(이원상)
Choi, Jae Young(최재영) ORCID logo https://orcid.org/0000-0001-9493-3458
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