title: Fucoidan promotes mechanosensory hair cell regeneration following amino glycoside-induced cell death.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Chung-Ang University, Seoul, South Korea.
authors.forename: In Seok
authors.initials: IS
authors.lastname: Moon
authors.forename: Ju-Hoon
authors.initials: JH
authors.lastname: So
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Jung
authors.forename: Won-Sang
authors.initials: WS
authors.lastname: Lee
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kim
authors.forename: Jung-Hwa
authors.initials: JH
authors.lastname: Choi
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Kim
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Choi
mesh_terms: D000617:Aminoglycosides / Q000633:toxicity*; D000818:Animals; D030801:Animals, Genetically Modified; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005346:Fibroblast Growth Factors / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007760:Labyrinth Supporting Cells / Q000187:drug effects / Q000473:pathology; D053403:Lateral Line System / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D040542:Mechanotransduction, Cellular / Q000187:drug effects*; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D009355:Neomycin / Q000633:toxicity*; D011134:Polysaccharides / Q000494:pharmacology*; D051880:Receptors, Notch / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology
chemical_list: D000617:Aminoglycosides; D011134:Polysaccharides; D051880:Receptors, Notch; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D005346:Fibroblast Growth Factors; C007789:fucoidan; D009355:Neomycin