Gasdermin D-Mediated Pyroptosis Exerts Two Opposite Effects of Resisting Enzymatic Digestion and Expanding Inflammatory Response in Acute Pancreatitis.

ABSTRACT: Gasdermin D (GSDMD)-induced pyroptosis is associated with inflammatory disease. However, the role of GSDMD in acute pancreatitis (AP) is not yet fully elucidated. This study reveals that GSDMD serves two distinct functions in pancreatic acinar cells and macrophages. In acinar cells, GSDMD inhibits the synthesis of pancreatic enzyme by downregulating the expression of Prss1, Pnlip, and Amy1 via the inhibition of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR)/ribosomal protein S6 (RPS6)/eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) pathway. Moreover, GSDMD induces pancreatic acinar cells to express mucin 1 (MUC1) by activating the nuclear factor kappa-B (NF-κB) pathway, which forms a barrier that prevents digestive enzyme-mediated digestion. However,

SUBMITTER: Liu C 

PROVIDER: S-EPMC12376566 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature