PUBLICATION HIGHLIGHT

NRF2 activates growth factor genes and downstream AKT signaling to induce mouse and human hepatomegaly

When uncontrolled and overabundant, a protein that protects against harmful oxidants appears to fuel liver enlargement and may be linked to host of metabolic conditions

In a new study, published February 24, 2020 in the Journal of Hepatology , a team of scientists, led by postdoctoral fellows Feng He, PhD, and Laura Antonucci, PhD, and senior author Michael Karin, PhD, Distinguished Professor of Pharmacology and Pathology at University of California San Diego School of Medicine, suggest prolonged exposure to NRF2 and KEAP1 may contribute to enlargement of the liver and fatty liver diseases.

The new findings, said Karin, suggest that AKT inhibitors, some of which have already been evaluated in humans for their anti-cancer activity, may be effective in the treatment and reversal of hepatomegaly, which affects more than 200 million persons worldwide.

Highlights of Study:

*  Liver p62 accumulation and constitutive NRF2 activation lead to liver lipid buildup, glycogen synthesis and hepatomegaly

*  NRF2 activation mediates transcriptional induction of PDGF and EGF receptor ligands that activate AKT

*   AKT and tyrosine kinase inhibitors block NRF2-mediated AKT activation and hepatomegaly

*   NRF2-AKT signaling is elevated in HSOS- and AIH-related human hepatomegaly

Dr. Karin is also the Project Leader of Project 1 for the UCSD Superfund Research Center in which this study was partially funded.

To read more about this research, please visit the study where it is published online in the Journal of Hepatology (February 24, 2020).

Media Source: UC San Diego Health News - News Release

Published study:

He F, Antonucci L, Yamachika S, Zhang Z, Taniguchi K, Umemura A, Hatzivassiliou G, Roose-Girma M, Reina-Campos M, Molina AD, Diaz-Meco MT, Moscat J, Sun B, Karin M. NRF2 Activates Growth Factor Genes and Downstream AKT Signaling to Induce Mouse and Human Hepatomegaly. Journal of Hepatology. 2019, Accepted.

For more information, please visit the following UCSD Superfund Research Project:

UCSD Superfund Research Center - Project 1 for the UCSD Superfund Research Center
Dr. Michael Karin
Distinguished Professor of Pharmacology, Ben and Wanda Hildyard Chair for Mitochondrial and Metabolic Diseases, American Cancer Society Research Professor at the University of California, San Diego