Pancreatic acinar cell fate relies on system x_C^- to prevent ferroptosis during stress.

ABSTRACT: Acinar cell dedifferentiation is one of the most notable features of acute and chronic pancreatitis. It can also be the initial step that facilitates pancreatic cancer development. In the present study, we further decipher the precise mechanisms and regulation using primary human cells and murine experimental models. Our RNAseq analysis indicates that, in both species, early acinar cell dedifferentiation is accompanied by multiple pathways related to cell survival that are highly enriched, and where SLC7A11 (xCT) is transiently upregulated. xCT is the specific subunit of the cystine/glutamate antiporter system x_C^-. To decipher its role, gene silencing, pharmacological inhibition and a knock-out mouse model were used. Acinar cells with depleted or reduced xCT function

SUBMITTER: Pan Z 

PROVIDER: S-EPMC10442358 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature