Publication: Role of fibrosis-related genes and pancreatic duct obstruction in rat pancreatitis models: Implications for chronic pancreatitis
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Date
2007
Authors
Miyauchi, M. ; Suda, K. ; Kuwayama, C. ; Abe, H. ; Kakinuma, C.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Human chronic pancreatitis is characterized
by irreversible fibrosis, whereas pancreatic fibrosis in
animal models is reversible. In this study, we compare
the development of pancreatic fibrosis in the dibutyltin
dichloride (DBTC) model, WBN/Kob rats and bile ductligated
(BDL) rats. DBTC (8 mg/kg) was administered
to LEW rats, and the pancreas was histopathologically
investigated sequentially. Male and female WBN/Kob
rats aged 4, 6 and 8 months were also examined. BDL
rats were prepared by ligation of the bile duct at the
duodenal portion and sacrificed at 3 or 7 days after
ligation. Fibrosis in the DBTC model peaked after 1
week and was limited to the areas around the pancreatic
ducts after 2 weeks, and was composed of both type I
and type III collagen. In contrast, fibrosis in male
WBN/Kob rats peaked at age 4 months, expanded into
intralobular area, and was composed of type III collagen.
It exhibited almost no type I collagen and a marked
tendency to regress. Pancreatic fibrosis in BDL rats was
somewhat difficult to induce and required increased
stimulation. This suggests that fibrosis in human biliary
pancreatitis may gradually form based on weak,
continuous stimulation. We conclude that type I collagen
may be involved in the progression of irreversible
fibrosis. The imbalance between synthesis and
degradation of extracellular matrix molecules or degree
of stimulation over a certain period may lead to
pancreatic fibrosis. Gene expressions of prolyl
hydroxylase and tissue inhibitors of matrix
metalloproteinase-2 were elevated.
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