Inhibiting xCT/SLC7A11 induces ferroptosis of myofibroblastic hepatic stellate cells but exacerbates chronic liver injury.

ABSTRACT:

Background & aims

The outcome of liver injury is dictated by factors that control the accumulation of myofibroblastic (activated) hepatic stellate cells (MF-HSCs) but therapies that specifically block this process have not been discovered. We evaluated the hypothesis that MF-HSCs and liver fibrosis could be safely reduced by inhibiting the cysteine/glutamate antiporter xCT.

Methods

xCT activity was disrupted in both HSC lines and primary mouse HSCs to determine its effect on HSC biology. For comparison, xCT expression and function were also determined in primary mouse hepatocytes. Finally, the roles of xCT were assessed in mouse models of liver fibrosis.

Results

We found that xCT mRNA levels were almost a log-fold higher in primary mouse HSCs than in primary mouse hep

SUBMITTER: Du K 

PROVIDER: S-EPMC8594404 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature