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Theranostics 2020; 10(13):5829-5844. doi:10.7150/thno.44051 This issue Cite

Research Paper

Activation of TFEB-mediated autophagy by trehalose attenuates mitochondrial dysfunction in cisplatin-induced acute kidney injury

Lingling Zhu*, Yujia Yuan*, Longhui Yuan, Lan Li, Fei Liu, Jingping Liu, Younan Chen, Yanrong Lu✉, Jingqiu Cheng✉

NHC Key Laboratory of Transplant Engineering and Immunology, Department of Nephrology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China
* Co-first author: These authors contributed equally to the authorship of this article

✉ Corresponding authors: Jingqiu Cheng: Key Laboratory of Transplant Engineering and Immunology, West China Hospital, No. 1 Keyuan 4th Road, Gaopeng Avenue, Chengdu 610041, People's Republic of China, Fax: +86 28 85164029; E-mail: jqchengedu.cn. More

Citation:
Zhu L, Yuan Y, Yuan L, Li L, Liu F, Liu J, Chen Y, Lu Y, Cheng J. Activation of TFEB-mediated autophagy by trehalose attenuates mitochondrial dysfunction in cisplatin-induced acute kidney injury. Theranostics 2020; 10(13):5829-5844. doi:10.7150/thno.44051. https://www.thno.org/v10p5829.htm
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Abstract

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Aims: Cisplatin, an anticancer drug, always leads to nephrotoxicity by causing mitochondrial dysfunction. As a major mechanism for cellular self-degradation, autophagy has been proven to protect against cisplatin-induced acute kidney injury (AKI). Based on the activation of autophagy induced by trehalose, we aimed to investigate the nephroprotective effects of trehalose on cisplatin-induced AKI and its underlying mechanisms.

Results: Due to the activation of autophagy, mitochondrial dysfunction (mitochondrial fragmentation, depolarization, reactive oxygen species (ROS), and reduced ATP generation) and apoptosis induced by cisplatin were markedly inhibited in trehalose-treated HK2 cells in vitro. Based on the transcriptional regulation role of transcription factor EB (TFEB) in autophagy and lysosome, we characterized trehalose-induced nuclear translocation of TFEB. Furthermore, consistent with trehalose treatment, overexpression of TFEB inhibited cell injury induced by cisplatin. However, the protective effects of trehalose were largely abrogated in tfeb-knockdown cells. In vivo, cisplatin injection resulted in severe kidney dysfunction and histological damage in mice. Trehalose administration activated TFEB-mediated autophagy, alleviated mitochondrial dysfunction and kidney injury in AKI mice.

Innovation and conclusion: Our data suggest that trehalose treatment preserves mitochondria function via activation of TFEB-mediated autophagy and attenuates cisplatin-induced kidney injury.

Keywords: autophagy, transcription factor EB, mitochondrial dysfunction, acute kidney injury, trehalose

Citation styles

APA
Zhu, L., Yuan, Y., Yuan, L., Li, L., Liu, F., Liu, J., Chen, Y., Lu, Y., Cheng, J. (2020). Activation of TFEB-mediated autophagy by trehalose attenuates mitochondrial dysfunction in cisplatin-induced acute kidney injury. Theranostics, 10(13), 5829-5844. https://doi.org/10.7150/thno.44051.

ACS
Zhu, L.; Yuan, Y.; Yuan, L.; Li, L.; Liu, F.; Liu, J.; Chen, Y.; Lu, Y.; Cheng, J. Activation of TFEB-mediated autophagy by trehalose attenuates mitochondrial dysfunction in cisplatin-induced acute kidney injury. Theranostics 2020, 10 (13), 5829-5844. DOI: 10.7150/thno.44051.

NLM
Zhu L, Yuan Y, Yuan L, Li L, Liu F, Liu J, Chen Y, Lu Y, Cheng J. Activation of TFEB-mediated autophagy by trehalose attenuates mitochondrial dysfunction in cisplatin-induced acute kidney injury. Theranostics 2020; 10(13):5829-5844. doi:10.7150/thno.44051. https://www.thno.org/v10p5829.htm

CSE
Zhu L, Yuan Y, Yuan L, Li L, Liu F, Liu J, Chen Y, Lu Y, Cheng J. 2020. Activation of TFEB-mediated autophagy by trehalose attenuates mitochondrial dysfunction in cisplatin-induced acute kidney injury. Theranostics. 10(13):5829-5844.

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