Chemistry

Cisplatin

TFEB

Chemotherapy

Trehalose

Cancer research

Biochemistry

Autophagy

Reactive oxygen species

Biology

Endocrinology

Apoptosis

Kidney

Programmed cell death

Cell biology

Acute kidney injury

Nephrotoxicity

Internal medicine

Mitochondrion

Pharmacology

Medicine

Theranostics

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.

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