Sa1863 Cd38/ADP Ribosyl Cyclase Mediates Bile Acid-Induced Ca2+ Signals and Acinar Cell Injury

Abstract

G A A b st ra ct s staining and western blot respectively. Acute pancreatitis was induced by ten injections of cerulein (50 μg/kg, i.p.) at hourly intervals. Mice were monitored for up to 7 days after induction of pancreatitis. Pancreatic injury was determined by measuring serum levels of amylase and examining pathologic changes of pancreas. For quantifying severity of tissue inflammation, we measured mRNA levels of myeloperoxidase (MPO, a marker of neutrophil infiltration) with real-time RT-PCR. Results: We found that MFG-E8 was constitutively expressed in murine pancreas. The protein was revealed to localize in pancreatic ductal epithelial cells. As expected, administration of cerulein induced acute pancreatitis ranging from the acute phase (i.e. 1 h after the final injection of cerulein) to recovery phase (i.e. up to 7 days after cerulein treatment) in WT mice. Pancreatic MFG-E8 was markedly increased 24 hours after induction of pancreatitis. The protein expression was maintained at high levels during the recovery phase. Using MFG-E8 KO mice, we found that MFG-E8 deficiency did not affect the severity of acute phase of cerulein-induced pancreatitis. However, pancreatic recovery following cerulein-induced pancreatitis was markedly delayed in the KO mice comparing to WT controls. Conclusions: Together, the data suggested that MFGE8 is a critical protein that protects against progression of acute pancreatitis. MFG-E8 deficiency impairs pancreatic recovery and it is needed in pancreatic recovery from pancreatitis. This novel finding may benefits the development of a potential novel molecular agent for pancreatitis therapy.