Objective The cerulein-induced mouse pancreatitis model is a well-established, commonly used representation of human chronic pancreatitis pathology. Although studies report sex-dependent differences in human chronic pancreatitis, there are no studies in this model directly comparing sex response to pancreatic injury and recovery. Therefore, we designed a study to investigate whether sex-dependent differences in chronic pancreatitis injury and recovery exist in the cerulein-induced pancreatitis model. Methods Adult male and female C57BL/6 mice were administered cerulein (50 mu g/kg, 5 hourly intraperitoneal injections/day, 3 days/week) for 4 weeks to induce chronic pancreatitis; control mice received normal saline injections. Pancreata and blood were harvested at 4 days (as injury group) or 4 weeks (as recovery group) after the last injection. Amylase secretion was measured from the serum. Acinar injury was scored on H&E sections. Fibrosis was assessed by Sirius Red and collagen immunofluorescence staining. Results Compared to time-matched controls, injury group displayed decreased body and pancreas weight, and increased acinar injury and fibrosis, with no significant differences between males and females. Recovery group demonstrated recovery of body weight, partial recovery of pancreas weight, reversal of acinar injury, and partial reversal of fibrosis, with no significant differences between males and females. Amylase secretion/body weight was similar across all groups. Conclusions Male and female mice of the cerulein-induced chronic pancreatitis demonstrate similar responses to chronic pancreatitis injury and recovery. Although this model may not sufficiently emulate sex-dependent responses in human chronic pancreatitis, our study supports that both sexes of mice from this model can be used for the study of chronic pancreatitis.

Objectives To investigate regulation of microRNA (miR)-200 family (a, b, c, 141, and 429) in chronic pancreatitis (CP). This was accomplished by examining miR-200 family levels in a mouse model in vivo and their regulation in pancreatic cells in vitro. Methods Chronic pancreatitis was induced by cerulein for 4 weeks (50 μg/kg, 5 hourly intraperitoneal injections/day, and 3 days/week). Control mice received normal saline. The pancreata were harvested for fibrosis assessment by Sirius red staining and for miRNA, collagen, and fibronectin levels by quantitative PCR. In vitro, human primary pancreatic stellate cells and human primary pancreatic fibroblast (hPFBs), and rat pancreatic epithelial AR42J cells were treated with vehicle, transforming growth factor (TGF)-β (1 ng/mL), or BMP2 (50 ng/mL) for 24 hours and then harvested for miRNA analysis. Results In CP, miR-200s were decreased by 56% to 70% and inversely correlated with pancreatic fibrosis, miR-21, and miR-31 (P < 0.05). In vitro, TGF-β inhibited miR-200b in AR42J cells by 62%, whereas BMP2 increased miR-200b in all 3 cell types in a range of 1.5- to 3.4-fold and inhibited miR-21 in hPFBs by 21% (P < 0.05). Conclusions Both in vivo and in vitro studies suggest an antifibrogenic function of miR-200s in CP. The TGF-β and BMP2 may function through inverse regulation of miR-200b levels.