Effect of JNK inhibitor SP600125 on hair cell regeneration in zebrafish ( Danio rerio ) larvae

// Yingzi He 1, 4, * , Chengfu Cai 2, * , Shaoyang Sun 3 , Xu Wang 3 , Wenyan Li 1 , Huawei Li 1, 5, 6 1 Department of Otorhinolaryngology, Key Laboratory of Hearing Science, Ministry of Health, EENT Hospital, Fudan University, Shanghai, China 2 Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital, Xiamen University, Xiamen, China 3 Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China 4 Laboratory Center, Affiliated Eye and ENT Hospital of Fudan University, Shanghai, China 5 Institute of Stem Cell and Regeneration Medicine, Institutions of Biomedical Science, Fudan University, Shanghai, China 6 Key Laboratory of Hearing Science, Ministry of Health, EENT Hospital, Fudan University, Shanghai, China * These authors contributed equally to this work Correspondence to: Huawei Li, email: hwli@shmu.edu.cn Keywords: JNK, SP600125, hair cell regeneration, zebrafish, Wnt Received: January 25, 2016      Accepted: June 29, 2016      Published: July 12, 2016 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.