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| Status |
Public on Jun 23, 2024 |
| Title |
A hepatocyte-specific transcriptional program driven by Rela and Stat3 exacerbates experimental colitis in mice by modulating bile synthesis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
RelA and Stat3, often collaboratively, induce the synthesis of an array of factors,which orchestrate multiorgan crosstalk in health and diseases. RelA and Stat3 functions in theintestinal epithelial cells are known to tune colon inflammation. If their hepatic activity also impacts inflammation in the gut remains unclear. Here, we reveal that the combined deficiency of RelA and Stat3 specifically in hepatocytes ameliorates DSS-induced experimental colitis. Our transcriptomics analyses identified that they activated a hepatic gene program, which directed the expression of alternate bile synthesis pathway genes. Our metabolomics studies substantiated that an absence of RelA and Stat3 in hepatocytes led to a reduced accumulation of inflammatory bile acids, particularly chenodeoxycholic acid, not only in the liver but also in the gut. Indeed, knockout mice displayed a lessened expression of only in the liver but also in the gut. Indeed, knockout mice displayed a lessened expression of inflammatory cytokines and a diminished recruitment of inflammatory cells in the gut upon colitogenic insults; on the other hand, supplementing chenodeoxycholic acid was sufficient to restore the colitogenic sensitivity in these mice. In sum, we suggest that the engagement of inflammatory transcription factors in distant tissues promotes intestinal pathologies via metabolic wiring.
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| Overall design |
Liver were obtained from WT and relaΔhepstat3Δhep mice, either left untreated or treated with 2% DSS for 6 days. mRNA levels in all four group with 3 biological replicates were generated via next generation sequencing.
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| Contributor(s) |
Gokhale RS, Mohanty D, Basak S, Nandicoori VK, Singh J, Sanyal P |
| Citation(s) |
39137024 |
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| Submission date |
Sep 15, 2023 |
| Last update date |
Sep 11, 2024 |
| Contact name |
Debasisa Mohanty |
| E-mail(s) |
deb@nii.ac.in
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| Organization name |
National Institute of Imunology
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| Street address |
Aruna Asaf Ali Marg
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| City |
New Delhi |
| ZIP/Postal code |
110067 |
| Country |
India |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA1017780 |
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