Akt1 and Akt2 Isoforms Play Distinct Roles in Regulating the Development of Inflammation and Fibrosis Associated with Alcoholic Liver Disease.

ABSTRACT: Akt kinase isoforms (Akt1, Akt2, and Akt3) have generally been thought to play overlapping roles in phosphoinositide 3-kinase (PI3K)-mediated-signaling. However, recent studies have suggested that they display isoform-specific roles in muscle and fat. To determine whether such isoform-specificity is observed with respect to alcoholic liver disease (ALD) progression, we examined the role of Akt1, Akt2, and Akt3 in hepatic inflammation, and pro-fibrogenic proliferation and migration using Kupffer cells, hepatic stellate cells (HSC), and hepatocytes in an ethanol and lipopolysaccharide (LPS)-induced two-hit model in vitro and in vivo. We determined that siRNA-directed silencing of Akt2, but not Akt1, significantly suppressed cell inflammatory markers in HSC and Kupffer cells. Although both Ak

SUBMITTER: Reyes-Gordillo K 

PROVIDER: S-EPMC6912497 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature