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

ABSTRACT:

Background & aims

Hepatomegaly can be triggered by insulin and insulin-unrelated etiologies. Insulin acts via AKT, but how other challenges cause hepatomegaly is unknown.

Methods

Since many hepatomegaly-inducing toxicants and stressors activate NRF2, we examined the effect of NRF2 activation on liver size and metabolism using a conditional allele encoding a constitutively active NRF2 variant to generate Nrf2^Act-hep mice in which NRF2 is selectively activated in hepatocytes. We also used adenoviruses encoding variants of the autophagy adaptor p62/SQSTM1, which activates liver NRF2, as well as liver-specific ATG7-deficient mice (Atg7^Δhep) and liver specimens from patients with hepatic sinusoidal obstruction syndrome (HSOS) and autoimmune hepatitis (AIH).

SUBMITTER: He F 

PROVIDER: S-EPMC8054878 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature