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Series GSE149172 Query DataSets for GSE149172
Status Public on Apr 24, 2020
Title The circadian clock gene Bmal1 facilitates cisplatin-induced renal injury and hepatization
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary 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 to cisplatin treatment, and the therapeutic intervention targeting Bmal1 in the kidney may be a promising strategy to minimize the toxic side-effects of cisplatin in its clinical applications.
Overall design Total RNA were isolated from HK-2 cells which were infected with adenovirus expressing either Bmal1 CDS domain or GFP and seqenced using Illumina HiSeq 3000
Contributor(s) Zha M, Tian T, Xu W, Liu S, Jia J, Wang L, Yan Q, Li N
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Submission date Apr 23, 2020
Last update date Apr 26, 2020
Contact name Jiangyi Yu
Organization name Affiliated Hospital of Nanjing University of Chinese Medicine
Street address No. 155, Hanzhong Rd
City Nanjing
ZIP/Postal code 210029
Country China
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (2)
GSM4491543 Ad-GFP
GSM4491544 Ad-Bmal1
BioProject PRJNA627591
SRA SRP258031

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Supplementary file Size Download File type/resource
GSE149172_RAW.tar 370.0 Kb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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