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Gastric inflammation, metaplasia, and tumor development in gastrin-deficient mice

Friis-Hansen, Lennart ; Rieneck, Klaus ; Nilsson, Hans-Olof LU ; Wadström, Torkel LU and Rehfeld, Jens F. (2006) In Gastroenterology 131(1). p.246-258
Abstract
Background & Aims: Gastrin deficiency and proton pump inhibitor treatment cause achlorhydria, which predisposes to disease. To elucidate the underlying molecular biology, we examined the changes in gastric gene expression in both types of achlorhydria. We also explored the associated changes in the gastric microflora and the long-term consequences of gastrin-deficient achlorhydria. Methods: Expression profiles were generated from gastric RNA from wild-type mice, gastrin knockout (KO) mice, gastrin KO mice after I week of gastrin infusion, and wild-type mice treated for I month with a proton pump inhibitor. The results were confirmed using real-time polymerase chain reaction and immuno-histochemistry. Selective media were used to... (More)
Background & Aims: Gastrin deficiency and proton pump inhibitor treatment cause achlorhydria, which predisposes to disease. To elucidate the underlying molecular biology, we examined the changes in gastric gene expression in both types of achlorhydria. We also explored the associated changes in the gastric microflora and the long-term consequences of gastrin-deficient achlorhydria. Methods: Expression profiles were generated from gastric RNA from wild-type mice, gastrin knockout (KO) mice, gastrin KO mice after I week of gastrin infusion, and wild-type mice treated for I month with a proton pump inhibitor. The results were confirmed using real-time polymerase chain reaction and immuno-histochemistry. Selective media were used to characterize the gastric microflora. Results: The number of gastric bacteria was increased in both gastrin KO and PPI-treated mice. The expression profiles revealed activation of immune defense genes, interferon-regulated response genes, and intestinal metaplasia of the gastric mucosa. In young gastrin-deficient mice, gastrin infusions reversed the changes. Over time, the changes accumulated, became irreversible, and progressed into metaplasia and polyp development. Finally, the study showed that gastrin regulated the expression of genes encoding extracellular matrix proteins. Conclusions: Independently of gastrin, achlorhydria is associated with gastric bacterial overgrowth and intestinal gene expression patterns and is associated with predisposition to disease. Gastrin is therefore essential for prevention of gastric disease, mainly through control of acid secretion but to a lesser extent also through control of gastric gene expression. The gastrin-deficient mouse serves as a useful new model for gastric metaplasia and neoplasia. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Gastroenterology
volume
131
issue
1
pages
246 - 258
publisher
Elsevier
external identifiers
  • wos:000238983300032
  • pmid:16831607
  • scopus:33745737786
ISSN
1528-0012
DOI
10.1053/j.gastro.2006.04.031
language
English
LU publication?
yes
id
cd95d340-5c78-49cd-80ef-9a779fdb67b9 (old id 402204)
date added to LUP
2016-04-01 12:28:58
date last changed
2021-07-21 03:26:48
@article{cd95d340-5c78-49cd-80ef-9a779fdb67b9,
  abstract     = {Background & Aims: Gastrin deficiency and proton pump inhibitor treatment cause achlorhydria, which predisposes to disease. To elucidate the underlying molecular biology, we examined the changes in gastric gene expression in both types of achlorhydria. We also explored the associated changes in the gastric microflora and the long-term consequences of gastrin-deficient achlorhydria. Methods: Expression profiles were generated from gastric RNA from wild-type mice, gastrin knockout (KO) mice, gastrin KO mice after I week of gastrin infusion, and wild-type mice treated for I month with a proton pump inhibitor. The results were confirmed using real-time polymerase chain reaction and immuno-histochemistry. Selective media were used to characterize the gastric microflora. Results: The number of gastric bacteria was increased in both gastrin KO and PPI-treated mice. The expression profiles revealed activation of immune defense genes, interferon-regulated response genes, and intestinal metaplasia of the gastric mucosa. In young gastrin-deficient mice, gastrin infusions reversed the changes. Over time, the changes accumulated, became irreversible, and progressed into metaplasia and polyp development. Finally, the study showed that gastrin regulated the expression of genes encoding extracellular matrix proteins. Conclusions: Independently of gastrin, achlorhydria is associated with gastric bacterial overgrowth and intestinal gene expression patterns and is associated with predisposition to disease. Gastrin is therefore essential for prevention of gastric disease, mainly through control of acid secretion but to a lesser extent also through control of gastric gene expression. The gastrin-deficient mouse serves as a useful new model for gastric metaplasia and neoplasia.},
  author       = {Friis-Hansen, Lennart and Rieneck, Klaus and Nilsson, Hans-Olof and Wadström, Torkel and Rehfeld, Jens F.},
  issn         = {1528-0012},
  language     = {eng},
  number       = {1},
  pages        = {246--258},
  publisher    = {Elsevier},
  series       = {Gastroenterology},
  title        = {Gastric inflammation, metaplasia, and tumor development in gastrin-deficient mice},
  url          = {http://dx.doi.org/10.1053/j.gastro.2006.04.031},
  doi          = {10.1053/j.gastro.2006.04.031},
  volume       = {131},
  year         = {2006},
}