@article{60021b0547bb4bd0ae54674296844116,
title = "p62/SQSTM1 by Binding to Vitamin D Receptor Inhibits Hepatic Stellate Cell Activity, Fibrosis, and Liver Cancer",
abstract = "Hepatic stellate cells (HSCs) play critical roles in liver fibrosis and hepatocellular carcinoma (HCC). Vitamin D receptor (VDR) activation in HSCs inhibits liver inflammation and fibrosis. We found that p62/SQSTM1, a protein upregulated in liver parenchymal cells but downregulated in HCC-associated HSCs, negatively controls HSC activation. Total body or HSC-specific p62 ablation potentiates HSCs and enhances inflammation, fibrosis, and HCC progression. p62 directly interacts with VDR and RXR promoting their heterodimerization, which is critical for VDR:RXR target gene recruitment. Loss of p62 in HSCs 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 HSCs, whose activation supports HCC.",
keywords = "fibrosis, hepatic stellate cells, hepatocellular carcinoma, inflammation, liver cancer, non-alcoholic steatohepatitis, nuclear receptors, p62, sequestosome-1, vitamin D receptor",
author = "Angeles Duran and Hernandez, {Eloy D.} and Miguel Reina-Campos and Castilla, {Elias A.} and Shankar Subramaniam and Sindhu Raghunandan and Roberts, {Lewis R.} and Tatiana Kisseleva and Michael Karin and Diaz-Meco, {Maria T.} and Jorge Moscat",
note = "Funding Information: Research was supported by grants from NIH ( R01DK108743 , R01CA172025 to J.M.; R01CA192642 to M.T.D.-M.; 5P30CA030199 to M.T.D-M. and J.M.; CCSPG Pilot Project Grant under award 5P30CA030199 to J.M.; R01CA163798 and R01CA118165 to M.K.), and the Superfund Basic Research Program P42ES010337 to M.K. We thank Robert F. Schwabe (Department of Medicine, Columbia University) for providing the LRat-Cre mouse line, and Dr. Jun Xu (University of California San Diego) for helping in the preparation of primary HSCs. We thank Diantha LaVine for the artwork, and Guillermina Garcia (Histology Core), Brian James (Genomics Core), and the personnel of the Cell Imaging, Animal Facility, and Viral Vectors Shared Resources at SBP for technical assistance. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = oct,
day = "10",
doi = "10.1016/j.ccell.2016.09.004",
language = "English (US)",
volume = "30",
pages = "595--609",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",
}