Aims
Acute pancreatitis (AP) is a severe pancreatic disorder that remains associated with high mortality due to a lack of effective drugs and management strategies. This study aimed to investigate the molecular pathogenic mechanisms of AP involving p53 and endoplasmic reticulum (ER) stress pathways.
Background and aims
Acute pancreatitis (AP) is a severe pancreatic disorder that remains associated with high mortality due to a lack of effective drugs and management strategies. This study aimed to investigate the molecular pathogenic mechanisms of AP involving p53 and endoplasmic reticulum (ER) stress pathways.
Conclusion
P53, which was activated by the ER stress pathway, promoted the progression of AP in mice expressing PRSS1 by inducing acinar cell apoptosis.
Methods
Expression of PRSS1 and p53 in human AP tissues was detected by immunohistochemistry and Western blotting. AP was induced with caerulein in humanized PRSS1 transgenic mice, and its severity was verified by histological imaging, evaluation of edema, serum amylase, and trypsin activity assays. A transferase-mediated d-UTP nick end-labeling assay was performed to evaluate acinar cell apoptosis associated with AP. The expression of ER stress genes was assessed by quantitative RT-PCR (qRT-PCR) and Western blotting.
Results
PRSS1 and p53 were highly expressed in human AP tissues. Expression of human PRSS1 in caerulein-treated mice induced significant acinar cell apoptosis and AP progression. P53 knockout significantly suppressed AP progression in humanized PRSS1 transgenic mice. The ER stress pathway was activated by PRSS1 and mediated the progression of AP in mouse pancreatic tissues. Application of a p53 inhibitor effectively ameliorated caerulein-induced AP in PRSS1 transgenic mice, while a p53 activator promoted the progression of AP.