A hedgehog survival pathway in 'undead' lipotoxic hepatocytes.

ABSTRACT:

Background & aims

Ballooned hepatocytes in non-alcoholic steatohepatitis (NASH) generate sonic hedgehog (SHH). This observation is consistent with a cellular phenotype in which the cell death program has been initiated but cannot be executed. Our aim was to determine whether ballooned hepatocytes have potentially disabled the cell death execution machinery, and if so, can their functional biology be modeled in vitro.

Methods

Immunohistochemistry was performed on human NASH specimens. In vitro studies were performed using HuH-7 cells with shRNA targeted knockdown of caspase 9 (shC9 cells) or primary hepatocytes from caspase 3(-/-) mice.

Results

Ballooned hepatocytes in NASH display diminished expression of caspase 9. This phenotype was modeled using shC9 cells; these c

SUBMITTER: Kakisaka K 

PROVIDER: S-EPMC3467008 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature