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GEO help: Mouse over screen elements for information. |
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| Status |
Public on May 01, 2024 |
| Title |
PCB126 Modifies the Murine Hepatic Transcriptome and Metallome to Promote Alcohol-associated Liver Disease Pathogenesis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: Environmental pollutants, including polychlorinated biphenyls (PCBs) have been shown to alter and promote the development of alcohol-associated liver disease (ALD). Our group recently demonstrated that PCB126 promoted steatosis, hepatomegaly, and modulated intermediary metabolism in an ALD rodent model. Objectives: To better understand how PCB126 promoted ALD, the current study adopts transcriptomic and metallomic approaches to identify mechanistic pathways involved in this promotion. Methods: Briefly, male C57BL/6J mice were exposed to 0.2 mg/kg PCB126 or corn oil vehicle prior to ethanol feeding in the chronic-binge model. Liver tissues were collected for RNA sequencing and ICP-MS metals quantification. Results: PCB126 uniquely modified the transcriptome in EtOH-fed mice in terms of variance. EtOH feeding alone resulting in >4000 differentially expressed genes (DEGs) and PCB126 exposure resulted in more DEGs in the EtOH-fed group over the pair-fed group. Top gene ontology (GO) biological processes indicated ‘peptidyl tyrosine modifications’ and GO molecular function processes showed a loss of ‘metal, and ion, and zinc binding’. Western blot analysis depicted that the JAK2-STAT5 signaling axis was disrupted by the enhanced loss of phosphorylated JAK2 in EtOH+PCB126 mice. Quantified liver essential metal levels were overall depleted by EtOH feeding, and potassium, magnesium, cobalt, and zinc were further decreased by PCB126. Discussion: The results suggests that phosphorylation and metal binding are disrupted in EtOH+PCB126 mice, implying that evolutionarily conserved homeostatic signaling mechanisms are modified by pollutant exposure in EtOH-fed mice. The loss of phosphorylation and essential metals are two suggestive modes of action that may explain the promotion of disease by PCB126 in ALD.
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| Overall design |
C57BL/6J mice were orally gavaged 0.2 mg/kg polychlorinated biphenyl 126 (PCB 126). Mice were then placed on the chronic-binge (ten-plus-one) alcohol (ethanol) feeding model using the Lieber-DeCarli Diet. Mice were initially allowed to acclimate to the diet over 5 days where mice were given 1 day of 0% ethanol, 2 days of 2% ethanol, and 2 days of 4% ethanol. Mice were then fed a 5% ethanol diet for 10 days. The following day (11th day - binge) mice were orally gavaged 5g/kg ethanol, followed by euthanasia and tissue collection. This study is an exact repeat of our characterization study previously published (PMID: 36377258)
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| Contributor(s) |
Gripshover TC, Wahlang B, Head KZ, Luo J, Bolatimi OE, Rouchka EC, Smith ML, Chariker JH, Cai L, Xu J, Cave MC |
| Citation(s) |
38619879 |
| Submission date |
Sep 29, 2023 |
| Last update date |
May 01, 2024 |
| Contact name |
Eric Christian Rouchka |
| E-mail(s) |
eric.rouchka@louisville.edu
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| Organization name |
University of Louisville
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| Department |
Biochemistry and Molecular Genetics
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| Lab |
KY INBRE Bioinformatics Core
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| Street address |
522 East Gray Street
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| City |
Louisville |
| State/province |
Kentucky |
| ZIP/Postal code |
40292 |
| Country |
USA |
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| Platforms (1) |
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| Samples (24)
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| GSM7814595 |
[Liver] [Pair-fed + Vehicle] [Replicate 1] |
| GSM7814596 |
[Liver] [Pair-fed + Vehicle] [Replicate 2] |
| GSM7814597 |
[Liver] [Pair-fed + Vehicle] [Replicate 3] |
| GSM7814598 |
[Liver] [Pair-fed + Vehicle] [Replicate 4] |
| GSM7814599 |
[Liver] [Pair-fed + Vehicle] [Replicate 5] |
| GSM7814600 |
[Liver] [Pair-fed + Vehicle] [Replicate 6] |
| GSM7814601 |
[Liver] [Pair-fed + PCB 126] [Replicate 1] |
| GSM7814602 |
[Liver] [Pair-fed + PCB 126] [Replicate 2] |
| GSM7814603 |
[Liver] [Pair-fed + PCB 126] [Replicate 3] |
| GSM7814604 |
[Liver] [Pair-fed + PCB 126] [Replicate 4] |
| GSM7814605 |
[Liver] [Pair-fed + PCB 126] [Replicate 5] |
| GSM7814606 |
[Liver] [Pair-fed + PCB 126] [Replicate 6] |
| GSM7814607 |
[Liver] [Ethanol-fed + Vehicle] [Replicate 1] |
| GSM7814608 |
[Liver] [Ethanol-fed + Vehicle] [Replicate 2] |
| GSM7814609 |
[Liver] [Ethanol-fed + Vehicle] [Replicate 3] |
| GSM7814610 |
[Liver] [Ethanol-fed + Vehicle] [Replicate 4] |
| GSM7814611 |
[Liver] [Ethanol-fed + Vehicle] [Replicate 5] |
| GSM7814612 |
[Liver] [Ethanol-fed + Vehicle] [Replicate 6] |
| GSM7814613 |
[Liver] [Ethanol-fed + PCB 126] [Replicate 1] |
| GSM7814614 |
[Liver] [Ethanol-fed + PCB 126] [Replicate 2] |
| GSM7814615 |
[Liver] [Ethanol-fed + PCB 126] [Replicate 3] |
| GSM7814616 |
[Liver] [Ethanol-fed + PCB 126] [Replicate 4] |
| GSM7814617 |
[Liver] [Ethanol-fed + PCB 126] [Replicate 5] |
| GSM7814618 |
[Liver] [Ethanol-fed + PCB 126] [Replicate 6] |
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| Relations |
| BioProject |
PRJNA1022507 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE244388_htseq_rawCounts.txt.gz |
916.9 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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