Oncotarget

Research Papers:

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

Yingzi He, Chengfu Cai, Shaoyang Sun, Xu Wang, Wenyan Li and Huawei Li _

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Oncotarget. 2016; 7:51640-51650. https://doi.org/10.18632/oncotarget.10540

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Abstract

Yingzi He1,4,*, Chengfu Cai2,*, Shaoyang Sun3, Xu Wang3, Wenyan Li1, Huawei Li1,5,6

1Department of Otorhinolaryngology, Key Laboratory of Hearing Science, Ministry of Health, EENT Hospital, Fudan University, Shanghai, China

2Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital, Xiamen University, Xiamen, China

3Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China

4Laboratory Center, Affiliated Eye and ENT Hospital of Fudan University, Shanghai, China

5Institute of Stem Cell and Regeneration Medicine, Institutions of Biomedical Science, Fudan University, Shanghai, China

6Key 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: [email protected]

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.


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