title: Effect of JNK inhibitor SP600125 on hair cell regeneration in zebrafish (Danio rerio) larvae.
abstract: The c-Jun amino-terminal kinase (JNK) proteins are a subgroup of the mitogen-activated protein kinase family. They play a complex role in cell proliferation, survival, and apoptosis. Here, we report a novel role of JNK signalling in hair cell regeneration. We eliminated hair cells of 5-day post-fertilization zebrafish larvae using neomycin followed by JNK inhibition with SP600125. JNK inhibition strongly decreased the number of regenerated hair cells in response to neomycin damage. These changes were associated with reduced proliferation. JNK inhibition also increased cleaved caspase-3 activity and induced apoptosis in regenerating neuromasts. Finally, JNK inhibition with SP600125 decreased the expression of genes related to Wnt. Over-activation of the Wnt signalling pathway partly rescued the hair cell regeneration defects induced by JNK inhibition. Together, our findings provide novel insights into the function of JNK and show that JNK inhibition blocks hair cell regeneration by controlling the Wnt signalling pathway.
authors.affiliation: Department of Otorhinolaryngology, Key Laboratory of Hearing Science, Ministry of Health, EENT Hospital, Fudan University, Shanghai, China.|Laboratory Center, Affiliated Eye and ENT Hospital of Fudan University, Shanghai, China.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, the First Affiliated Hospital, Xiamen University, Xiamen, China.
authors.forename: Chengfu
authors.initials: C
authors.lastname: Cai
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Shaoyang
authors.initials: S
authors.lastname: Sun
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Otorhinolaryngology, Key Laboratory of Hearing Science, Ministry of Health, EENT Hospital, Fudan University, Shanghai, China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology, Key Laboratory of Hearing Science, Ministry of Health, EENT Hospital, Fudan University, Shanghai, China.|Institute of Stem Cell and Regeneration Medicine, Institutions of Biomedical Science, Fudan University, Shanghai, China.|Key Laboratory of Hearing Science, Ministry of Health, EENT Hospital, Fudan University, Shanghai, China.
authors.forename: Huawei
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004625:Embryo, Nonmammalian; D006197:Hair / Q000166:cytology / Q000187:drug effects*; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D007814:Larva; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012038:Regeneration / Q000187:drug effects*; D015027:Zebrafish / Q000196:embryology
chemical_list: D000873:Anthracenes; D047428:Protein Kinase Inhibitors; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases
keywords: JNK; SP600125; Wnt; zebrafish; hair cell regeneration