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TFF2/SP-deficient mice show decreased gastric proliferation, increased acid secretion, and increased susceptibility to NSAID injury
James J. Farrell, … , Daniel K. Podolsky, Timothy C. Wang
James J. Farrell, … , Daniel K. Podolsky, Timothy C. Wang
Published January 15, 2002
Citation Information: J Clin Invest. 2002;109(2):193-204. https://doi.org/10.1172/JCI12529.
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Article

TFF2/SP-deficient mice show decreased gastric proliferation, increased acid secretion, and increased susceptibility to NSAID injury

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Abstract

Trefoil factor family 2 (TFF2), also known as spasmolytic polypeptide, is a member of the trefoil family of peptides and is expressed primarily in the mucous neck cells of the gastric mucosa. To study the physiologic role of TFF2, we have generated TFF2-deficient mice through targeted gene disruption. Homozygous mutant mice were viable and fertile without obvious gastrointestinal abnormalities. However, quantitative measurements revealed a significant decrease in gastric mucosal thickness and in gastric mucosal proliferation rates. In addition, there was a twofold increase in activated parietal cells resulting in a twofold increase in basal and stimulated gastric acid output and an undetectable serum gastrin level. The TFF2-deficient mice also showed a significant increase in the degree of gastric ulceration after administration of indomethacin. Taken together, these results suggest a physiologic role for TFF2 to promote mucosal healing through the stimulation of proliferation and downregulation of gastric acid secretion.

Authors

James J. Farrell, Douglas Taupin, Theodore J. Koh, Duan Chen, Chun-Mei Zhao, Daniel K. Podolsky, Timothy C. Wang

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Figure 6

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Role for TFF2/SP in gastric physiology and disease. In the setting of in...
Role for TFF2/SP in gastric physiology and disease. In the setting of injury and/or chronic Helicobacter pylori infection, increased TFF2 expression and secretion may stimulate proliferation and inhibit acid secretion. This would promote wound healing, but also contribute directly to increased gastric cancer risk.

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