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| Status |
Public on Nov 23, 2016 |
| Title |
p62/SQSTM1 by binding to vitamin D receptor inhibits hepatic stellate cell activity, fibrosis and liver cancer |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Hepatic stellate cells (HSC) play critical roles in liver fibrosis and hepatocellular carcinoma (HCC). Vitamin D receptor (VDR) activation in HSC inhibits liver inflammation and fibrosis. Here we show that p62/SQSTM1, a protein that is upregulated in liver parenchymal cells but downregulated in HCC-associated HSC, negatively regulates HSC activation. Total body or HSC-specific p62 ablation potentiates HSC activation and enhances inflammation, fibrosis and HCC progression. We demonstrate that p62 directly interacts with VDR and RXR promoting their heterodimerization, which is critical for VDR:RXR target genes recruitment. Loss of p62 in HSC impairs the repression of fibrosis and inflammation by VDR agonists. This demonstrates that p62 is a negative regulator of liver inflammation and fibrosis through its ability to promote VDR signaling in HSC, whose activation supports HCC development.
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| Overall design |
RNA was extracted from liver tissue from WT or p62KO mice previously injected with DEN and fed with HFD. Mouse Hepatic Stellate Cells (HSC) from WT or p62KO livers were extracted, immortalized with SV40 Ag (LVP016-Bsd, Genetarget) and cultured in-vitro with or without Calcipotriol for the indicated time points.
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| Contributor(s) |
Duran A, Hernandez ED, Reina-Campos M, Castilla EA, Subramanian S, Raghunandan S, Roberts LR, Kisseleva T, Karin M, Diaz-Meco MT, Moscat J |
| Citation(s) |
27728806 |
| Submission date |
Feb 29, 2016 |
| Last update date |
Jul 07, 2022 |
| Contact name |
Jorge Moscat |
| E-mail(s) |
jom4010@med.cornell.edu
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| Organization name |
WEILL CORNELL MEDICINE
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| Department |
Pathology and Laboratory Medicine
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| Lab |
Moscat and Diaz-Meco
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| Street address |
1188 York Avenue
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA313444 |
| SRA |
SRP070948 |
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