TAK1 deficiency promotes liver injury and tumorigenesis via ferroptosis and macrophage cGAS-STING signalling.

ABSTRACT:

Background & aims

Oxidative stress-mediated ferroptosis and macrophage-related inflammation play an important role in various liver diseases. Here, we explored if and how hepatocyte ferroptosis regulates macrophage stimulator of interferon genes (STING) activation in the development of spontaneous liver damage, fibrosis, and tumorigenesis.

Methods

We used a transforming growth factor-beta-activated kinase 1 (TAK1) deficiency-induced model of spontaneous liver damage, fibrosis, and tumorigenesis to investigate hepatocyte ferroptosis and its impact on macrophage STING signalling. Primary hepatocytes and macrophages were used for in vitro experiments.

Results

Significant liver injury and increased numbers of intrahepatic M1 macrophages were found in hepatocyte-spe

SUBMITTER: Su W 

PROVIDER: S-EPMC10033999 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature