title: Protection against chronic pancreatitis and pancreatic fibrosis in mice overexpressing pancreatic secretory trypsin inhibitor.
abstract: OBJECTIVE
  Mutations in the gene encoding for pancreatic secretory trypsin inhibitor (PSTI) can contribute to chronic pancreatitis. In the current study, we tested whether overexpression of PSTI-I in mice protects against chronic pancreatitis and pancreatic fibrosis.
  
  
  METHODS
  Rat PSTI-I expression was targeted to pancreatic acinar cells in transgenic mice. Chronic pancreatitis was achieved by intraperitoneal injection of cerulein for 10 weeks. Pancreatitis severity was assessed by histological grading of inflammatory infiltrate, atrophy, and fibrosis; quantitation of myeloperoxidase (MPO) activity; quantitative morphometric analysis of collagen content; and measurements of type I collagen, fibronectin, and transforming growth factor beta mRNA expression.
  
  
  RESULTS
  Cerulein administration to nontransgenic mice produced histological evidence of inflammatory infiltrate, glandular atrophy, and parenchymal fibrosis and increased collagen production, MPO activity, and collagen I and fibronectin mRNA levels. In cerulein-treated PSTI transgenic mice, there were significant reductions in inflammatory infiltrate, MPO activity, fibrosis, and collagen I and fibronectin mRNA levels. Transgenic mice treated with cerulein had significantly less collagen than nontransgenic mice.
  
  
  CONCLUSIONS
  The severity of chronic pancreatitis and pancreatic fibrosis is significantly reduced in mice expressing rat PSTI-I. We propose that pancreatic trypsin inhibitors play a protective role in the pancreatic response to repeated injurious events.
authors.affiliation: Department of Surgery, Duke University and Durham VA Medical Centers, Durham, NC, USA.
authors.forename: Jaimie D
authors.initials: JD
authors.lastname: Nathan
authors.forename: Joelle
authors.initials: J
authors.lastname: Romac
authors.forename: Ruth Y
authors.initials: RY
authors.lastname: Peng
authors.forename: Michael
authors.initials: M
authors.lastname: Peyton
authors.forename: Don C
authors.initials: DC
authors.lastname: Rockey
authors.forename: Rodger A
authors.initials: RA
authors.lastname: Liddle
mesh_terms: D000818:Animals; D002108:Ceruletide; D003094:Collagen / Q000378:metabolism; D024042:Collagen Type I / Q000235:genetics; D005353:Fibronectins / Q000235:genetics; D005355:Fibrosis; D020869:Gene Expression Profiling; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D012720:Severity of Illness Index; D016212:Transforming Growth Factor beta / Q000235:genetics; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: D024042:Collagen Type I; D005353:Fibronectins; D036341:Intercellular Signaling Peptides and Proteins; C504705:Spink1 protein, rat; D016212:Transforming Growth Factor beta; D014359:Trypsin Inhibitor, Kazal Pancreatic; D002108:Ceruletide; D003094:Collagen; D009195:Peroxidase