Adipose stem cells attenuate apoptosis by regulating C/EBP-homologous protein transcriptional activity in canines with acute pancreatitis.

Abstract

BACKGROUND: Acute pancreatitis (AP) is a common and serious digestive disease in dogs, and its high recurrence rate and complications pose a serious impact on canine health. The aim of this study was to investigate the mechanism by which adipose-derived stem cells (ADSCs) alleviate apoptosis by regulating C/EBP-homologous protein (CHOP) transcriptional activity in dogs with AP and AR42J cells. METHODS: Canine AP model was established using sodium taurocholate and trypsin, and treated with intravenous injection of ADSCs and conditioned medium (CM), pancreatic histopathological, ultrastructural changes, endoplasmic reticulum stress (ERS) and apoptosis markers, and apoptosis positivity rates were measured. In addition, the changing pattern of CHOP transcriptional activity was investigated by lipopolysaccharide (LPS) induced cellular inflammation model in vitro. RESULTS: The results showed that AP induced significant hemorrhage, inflammatory cell infiltration, cellular chromatin sequestration in pancreatic tissues, resulting in a significant upregulation of ERS and apoptosis markers, in addition to promoting the nuclear translocation and activation of CHOP transcriptional activity (P&#xa0;<&#xa0;0.05). In both in vitro and in vivo inflammatory models, ADSC treatment reduced the expression of ERS and apoptosis-related proteins and inhibited CHOP transcriptional activity (P&#xa0;<&#xa0;0.05). Targeted regulation of CHOP transcriptional activity effectively alleviated pancreatic cell apoptosis. CONCLUSIONS: ADSCs alleviate pancreatic cell apoptosis by inhibiting CHOP nuclear translocation and transcriptional activity. This finding provides a new strategy for the targeted medications for the treatment of canine AP.