Recombinant Reg3α protein protects against experimental acute pancreatitis in mice

Regenerating gene 3α (Reg3α) protein is a trophic factor that stimulates cell and tissue proliferation, neogenesis and also acts against apoptosis and necrosis. In order to explore the potential roles of recombinant Reg3α (rReg3α), we produced a mature rReg3α polypeptide for direct administration in l-arginine (L-Arg) induced acute pancreatitis (AP) in mice. Our results showed that rReg3α stimulated cell proliferation through Erk1/2 and p38 phosphorylation and also cyclin D1 upregulation mediated by Akt/ATF-2 signaling. Moreover, rReg3α administration significantly reduced the pancreatic damage caused by L-Arg injection, as shown in histological examination and serum amylase, lipase and C-reactive protein (CRP) assays. Not only acinar cell necrosis but also apoptosis found in the pancreas of AP mice were alleviated by rReg3α. Finally, upregulated Bcl-2 and Bcl-xL and suppressed poly (ADP-ribose) synthetase/polymerase (PARP) levels were detected as being relevant to the mechanism of rReg3α protection. We therefore conclude that rReg3α acts as a protective polypeptide against AP in mice by enhancing Bcl-2 and Bcl-xL expressions and suppressing PARP level.