Abstract LB568: Protein phosphatase 4 deficiency protects mice against cerulein-induced acute pancreatitis

Abstract

Abstract Background: Pancreatitis is an inflammatory disease of the pancreas that causes significant morbidity and mortality and is one of the major risk factors for pancreatic cancer. Protein phosphatase 4 (PP4) has been reported to be overexpressed in breast, lung and pancreatic cancers. PP4 plays an important role in the regulation of centrosome maturation, DNA repair, NF-κB, and c-jun-NH2-kinase (JNK) signaling pathways. However, the expression and functions of PP4 in pancreatitis have not been studied. Methods: To examine the functions of PP4 in cerulein-induced acute pancreatitis (AP), we crossed PP4flox/+ mice with pancreatic acinar cell specific cre, CreERT, which was driven by a full length pancreatic acinar specific elastase I promoter. PP4flox/flox, CreERT mice and control mice were treated with 8 hourly intraperitoneal injections of cerulein (50 µg/kg/h). The pancreata were harvested at different time points for histopathological examination and molecular analysis. Results: PP4 expression was increased at both protein and mRNA levels in mouse pancreas with AP. Compared to CreERT mice, PP4flox/flox, CreERT mice demonstrated significantly less edema, less inflammation, less necrosis or loss of pancreatic acinar cells in pancreas after cerulein treatment. The serum amylase and lipase levels were lower in cerulein-treated PP4flox/flox, CreERT mice compared with controls. The pancreata of PP4flox/flox, CreERT mice exhibited decreased STAT3 Tyr705 phosphorylation and decreased NF-κB activation cerulein-treated PP4flox/flox, CreERT mice than control mice. Conclusion: Our findings demonstrated that PP4 plays an important role in cerulein-induced AP through STAT3 and NF-κB signaling pathways. Inhibition of PP4 may help to reduce the pancreatic injuries and to prevent the development of chronic pancreatitis, which increases the risk of pancreatic cancer. Citation Format: Hua Wang, Reza Abbasgholizadeh, Rohan Moniruzzaman, Baoan Ji, Anirban Maitra, Huamin Wang. Protein phosphatase 4 deficiency protects mice against cerulein-induced acute pancreatitis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB568.