Protection against chronic pancreatitis and pancreatic fibrosis in mice overexpressing pancreatic secretory trypsin inhibitor.

Published

Journal Article

OBJECTIVES: 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.

Full Text

Duke Authors

Cited Authors

  • Nathan, JD; Romac, J; Peng, RY; Peyton, M; Rockey, DC; Liddle, RA

Published Date

  • January 2010

Published In

Volume / Issue

  • 39 / 1

Start / End Page

  • e24 - e30

PubMed ID

  • 19904222

Pubmed Central ID

  • 19904222

Electronic International Standard Serial Number (EISSN)

  • 1536-4828

Digital Object Identifier (DOI)

  • 10.1097/MPA.0b013e3181bc45e9

Language

  • eng

Conference Location

  • United States