title: Time-course proteomic analysis of taurocholate-induced necrotizing acute pancreatitis.
abstract: Acute pancreatitis is an inflammatory disease of the pancreas, which varies greatly in course and severity. Severe forms are associated with serious local and/or systemic complications, and eventually death. The pathobiology of acute pancreatitis is complex. Animal models have been developed to investigate pathobiological processes and identify factors determining disease course. We performed a time-course proteomic analysis using a rat model of severe necrotizing acute pancreatitis induced by taurocholate perfusion in the pancreatic ducts. Results showed that levels of proteins associated to a given biological process changed in a coordinated fashion after disease onset. It was possible to follow the response of a particular pathobiological process to pancreatitis induction and to compare the course of protein pathways. Proteins involved in acinar cell secretion were found to follow a different kinetics than other cellular processes. After an initial decrease, secretory pathway-associated proteins raised again at 18 h post-induction. This phenomenon coincided with a burst in the expression of pancreatitis-associated protein (REG3A), an acute phase protein produced by the exocrine pancreas, and with the decrease of classical markers of pancreatic injury, suggesting that the expression of proteins associated to the secretory pathway may be a modulating factor of pancreas injury.
  
  
  CONCLUSIONS
  Acute pancreatitis (AP) is a complex inflammatory disease, the pathobiology of which is not yet fully understood. Various animal models, relying on different mechanisms of disease induction, have been developed in order to investigate pathobiological processes of AP. In this study, we performed a time-course proteomic analysis to investigate changes of the pancreas proteome occurring in an experimental model of AP induced by perfusion of taurocholate, a bile acid, into the pancreatic duct. This experimental model is characterized by a severe disease with pancreatic necrosis and systemic inflammation. The objectives of this study were to determine the kinetics of functionally related proteins in the early steps of the experimental disease in order to identify protein pathways playing key roles in AP pathobiology and to correlate these data with parameters classically used to assess disease severity. The present work provides for the first time an overview of protein expression in the pancreas during the course of taurocholate-induced necrotizing AP. We believe that correlation of these results with data obtained using proteomic or biochemical approaches in various experimental models of AP will help in highlighting new features, generating hypotheses and constitute therefore a strong and reliable basis for further targeted investigations.
authors.affiliation: Biomedical Proteomics Research Group, Department of Human Protein Science, Geneva Faculty of Medicine, Geneva, Switzerland.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Fétaud-Lapierre
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Pastor
authors.forename: Manuel
authors.initials: M
authors.lastname: Jorge-Costa
authors.forename: Denis F
authors.initials: DF
authors.lastname: Hochstrasser
authors.forename: Denis R
authors.initials: DR
authors.lastname: Morel
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Frossard
authors.forename: Pierre
authors.initials: P
authors.lastname: Lescuyer
mesh_terms: D061354:Acinar Cells / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000951:Antigens, Neoplasm; D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002756:Cholagogues and Choleretics / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D037181:Lectins, C-Type; D008297:Male; D046790:Pancreas, Exocrine / Q000378:metabolism* / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000073718:Pancreatitis-Associated Proteins; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid / Q000009:adverse effects* / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D014408:Biomarkers, Tumor; D002756:Cholagogues and Choleretics; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; C000612146:Reg3a protein, rat; C000612144:Reg3b protein, rat; D013656:Taurocholic Acid