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Series GSE78760 Query DataSets for GSE78760
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
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.
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.
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
Department Pathology and Laboratory Medicine
Lab Moscat and Diaz-Meco
Street address 1188 York Avenue
City New York
State/province NY
ZIP/Postal code 10065
Country USA
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (14)
GSM2075766 WT-1
GSM2075767 WT-2
GSM2075768 WT-3
BioProject PRJNA313444
SRA SRP070948

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Supplementary file Size Download File type/resource
GSE78760_HSC_FPKM.xlsx 1.3 Mb (ftp)(http) XLSX
GSE78760_MiceLivers.xlsx 1.0 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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