DNA sensing and associated type 1 interferon signaling contributes to progression of radiation-induced liver injury.

ABSTRACT: Liver damage upon exposure to ionizing radiation (IR), whether accidental or therapeutic, can contribute to liver dysfunction. Currently, radiotherapy (RT) is used for various cancers including hepatocellular carcinoma (HCC); however, the treatment dose is limited by radiation-induced liver disease (RILD) with a high mortality rate. Furthermore, the precise molecular mechanisms of RILD remain poorly understood. Here, we investigated RILD pathogenesis using various knockout mouse strains subjected to whole-liver irradiation. We found that hepatocytes released a large quantity of double-stranded DNA (dsDNA) after irradiation. The cGAS-STING pathway in non-parenchymal cells (NPCs) was promptly activated by this dsDNA, causing interferon (IFN)-I production and release and concomitant hepatocyt

SUBMITTER: Du S 

PROVIDER: S-EPMC8245603 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature