Thiopurines impair the apical plasma membrane expression of CFTR in pancreatic ductal cells via RAC1 inhibition.

ABSTRACT:

Background and aims

Thiopurine-induced acute pancreatitis (TIP) is one of the most common adverse events among inflammatory bowel disease patients treated with azathioprine (AZA), representing a significant clinical burden. Previous studies focused on immune-mediated processes, however, the exact pathomechanism of TIP is essentially unclear.

Methods

To model TIP in vivo, we triggered cerulein-induced experimental pancreatitis in mice receiving a daily oral dose of 1.5 mg/kg AZA. Also, freshly isolated mouse pancreatic cells were exposed to AZA ex vivo, and acinar cell viability, ductal and acinar Ca²⁺ signaling, ductal Cl^- and HCO₃^- secretion, as well as cystic fibrosis transmembrane conductance regulator (CFTR) expression were ass

SUBMITTER: Tel B 

PROVIDER: S-EPMC9825359 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature