Biochemical analyses of cystatin-C dimers and cathepsin-B reveals a trypsin-driven feedback mechanism in acute pancreatitis.

ABSTRACT: Acute pancreatitis (AP) is characterised by self-digestion of the pancreas by its own proteases. This pathophysiological initiating event in AP occurs inside pancreatic acinar cells where intrapancreatic trypsinogen becomes prematurely activated by cathepsin B (CTSB), and induces the digestive protease cascade, while cathepsin L (CTSL) degrades trypsin and trypsinogen and therefore prevents the development of AP. These proteases are located in the secretory compartment of acinar cells together with cystatin C (CST3), an endogenous inhibitor of CTSB and CTSL. The results are based on detailed biochemical analysis, site-directed mutagenesis and molecular dynamics simulations in combination with an experimental disease model of AP using CST3 deficient mice. This identifies that CST3 is a crit

SUBMITTER: Modenbach JM 

PROVIDER: S-EPMC11833081 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature