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| Status |
Public on Sep 07, 2022 |
| Title |
Hepatic CYP2B10 is highly induced by binge ethanol and contributes to acute-on-chronic alcohol-induced liver injury |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
We altered the NIAAA (Gao Binge Model) of 8 week chronic plus binge ethanol (E8G1) to have 3 total ethanol gavages (5 g/kg; 1 every 24h) of ethanol after 8 weeks of chronic ethanol feeding (E8G3) to determine how the liver responds to chronic plus consecutive binge ethanol. Surprisingly, E8G3 treatment induced lower levels of liver injury, steatosis, inflammation, and fibrosis as compared to mice after E8G1 treatment. Microarray analyses were performed, identifying several pathways that may contribute to the observed liver adaptation to binge ethanol. In addition, cytochrome P450 2B10 (Cyp2b10) was a top upregulated gene in the E8G1 group and further upregulated in the E8G3 group, but only moderately induced after chronic ethanol consumption, which was confirmed by RT-qPCR and western blot analyses. Genetic disruption of the Cyp2b10 gene worsened liver injury in E8G1 and E8G3 mice with higher blood ethanol levels compared to wild-type control mice, while in vitro experimentation revealed that CYP2b10 did not directly promote ethanol metabolism. Metabolomic analyses revealed significant differences in hepatic metabolites from E8G1-treated Cyp2b10 KO and WT mice, and these metabolic alterations may contribute to the reduced liver injury in Cyp2b10 KO mice.
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| Overall design |
This experiment was conducted in parallel with GSE67546 - the E8w3B group is being uploaded in this dataset.
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| Contributor(s) |
Bryan M, Ming-Jiang X, Bin G |
| Citation(s) |
36224745 |
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| Submission date |
Sep 06, 2022 |
| Last update date |
Dec 07, 2022 |
| Contact name |
Bryan Mackowiak |
| E-mail(s) |
bryan.mackowiak@nih.gov
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| Phone |
3018270242
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| Organization name |
NIH
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| Street address |
5625 Fishers Lane, 2S12
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| City |
Rockville |
| State/province |
MD |
| ZIP/Postal code |
20852 |
| Country |
USA |
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| Platforms (1) |
| GPL7202 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA877202 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE212755_RAW.tar |
21.9 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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