The circadian clock gene Bmal1 facilitates cisplatin-induced renal injury and hepatization.

Cell Death & Disease
Min ZhaLiji Huang

Abstract

Cisplatin is one of the most potent chemotherapy drugs to treat cancers, but its clinical application remains limited due to severe nephrotoxicity. Several approaches have been developed to minimize such side effects, notably including chronotherapy, a well-known strategy based on the circadian clock. However, the component of the circadian clock machinery that particularly responses to the cisplatin stimulation remains unknown, including its functions in cisplatin-induced renal injury. In our present study, we demonstrated that Bmal1, as a key clock gene, was induced by the cisplatin stimulation in the mouse kidney and cultured human HK-2 renal cells. Gain- and loss-of-function studies indicated that Bmal1 facilitated cisplatin-induced renal injury both in vivo and in vitro, by aggravating the cell apoptotic process. More importantly, RNA-seq analysis revealed that Bmal1 triggered the expression of hallmark genes involved in renal hepatization, a critical event accompanied by the injury. At the molecular level, Bmal1 activated the transcription of hepatization-associated genes through direct recruitment to the E-box motifs of their promoters. Our findings suggest that Bmal1, a pivotal mediator induced renal injury in response ...Continue Reading

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Citations

Apr 5, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jiayang ZhangLihong Chen
Dec 9, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Nícia Reis SousaMaria João Valente

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Methods Mentioned

BETA
RNA-seq
Flow cytometry
ELISA
transfection
immunoprecipitation
ChIP
PCR
transfections

Software Mentioned

AlphaEaseFC
GraphPad Prism

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