Title: p62/SQSTM1 by binding to vitamin D receptor inhibits hepatic stellate cell activity, fibrosis and liver cancer

Accession Number: GSE78760

Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE78760

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Experiment Type(s): Array expression profiling by high throughput sequencing

Organism(s): Mus musculus

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.

Publication(s) associated with this dataset:

• Duran A, Hernandez ED, Reina-Campos M, Castilla EA, Subramaniam S, Raghunandan S, Roberts LR, Kisseleva T, Karin M, Diaz-Meco MT, Moscat J. 2016. p62/SQSTM1 by binding to vitamin D receptor inhibits hepatic stellate cell activity, fibrosis, and liver cancer. Cancer Cell 30(4):595-609. doi:10.1016/j.ccell.2016.09.004 PMID:27728806 PMCID:PMC5081228