title: Recombinant Reg3α protein protects against experimental acute pancreatitis in mice.
abstract: 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.
authors.affiliation: School of Life Science & Technology, China Pharmaceutical University, Nanjing, China.
authors.forename: Lu-Ting
authors.initials: LT
authors.lastname: Yu
authors.affiliation: School of Life Science & Technology, China Pharmaceutical University, Nanjing, China.
authors.forename: Meng-Qi
authors.initials: MQ
authors.lastname: Yang
authors.affiliation: Fraser Laboratories for Diabetes Research, Department of Medicine, McGill University Health Centre, Montreal, Canada.
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Liu
authors.affiliation: School of Life Science & Technology, China Pharmaceutical University, Nanjing, China.
authors.forename: Martin O
authors.initials: MO
authors.lastname: Alfred
authors.affiliation: School of Life Science & Technology, China Pharmaceutical University, Nanjing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Life Science & Technology, China Pharmaceutical University, Nanjing, China.
authors.forename: Xue-Qing
authors.initials: XQ
authors.lastname: Zhang
authors.affiliation: School of Life Science & Technology, China Pharmaceutical University, Nanjing, China; State Key Laboratory of Nature Medicines China Pharmaceutical University, Nanjing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Life Science & Technology, China Pharmaceutical University, Nanjing, China.
authors.forename: Ming-Yuan
authors.initials: MY
authors.lastname: Wu
authors.affiliation: School of Life Science & Technology, China Pharmaceutical University, Nanjing, China; State Key Laboratory of Nature Medicines China Pharmaceutical University, Nanjing, China. Electronic address: minwang@cpu.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: School of Life Science & Technology, China Pharmaceutical University, Nanjing, China; State Key Laboratory of Nature Medicines China Pharmaceutical University, Nanjing, China. Electronic address: chenluo@cpu.edu.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Luo
mesh_terms: D061354:Acinar Cells / Q000187:drug effects; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001120:Arginine / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D037181:Lectins, C-Type / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010195:Pancreatitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000073718:Pancreatitis-Associated Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C000612141:REG3A protein, human; D011994:Recombinant Proteins; D001120:Arginine
keywords: Acute pancreatitis; Necrosis; Pancreatic acini; Reg3α protein; l-arginine