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

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

Research output: Contribution to journalArticle

177 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)193-204
Number of pages12
JournalJournal of Clinical Investigation
Volume109
Issue number2
DOIs
StatePublished - 2002

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Non-Steroidal Anti-Inflammatory Agents
Stomach
Acids
Wounds and Injuries
Gastric Acid
Gastrins
Gastric Mucosa
Indomethacin
Trefoil Factor-2
Neck
Down-Regulation
Serum
Genes

ASJC Scopus subject areas

  • Medicine(all)

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TFF2/SP-deficient mice show decreased gastric proliferation, increased acid secretion, and increased susceptibility to NSAID injury. / Farrell, James J.; Taupin, Douglas; Koh, Theodore J.; Chen, Duan; Zhao, Chun Mei; Podolsky, Daniel K M; Wang, Timothy C.

In: Journal of Clinical Investigation, Vol. 109, No. 2, 2002, p. 193-204.

Research output: Contribution to journalArticle

Farrell, James J. ; Taupin, Douglas ; Koh, Theodore J. ; Chen, Duan ; Zhao, Chun Mei ; Podolsky, Daniel K M ; Wang, Timothy C. / TFF2/SP-deficient mice show decreased gastric proliferation, increased acid secretion, and increased susceptibility to NSAID injury. In: Journal of Clinical Investigation. 2002 ; Vol. 109, No. 2. pp. 193-204.
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AU - Podolsky, Daniel K M

AU - Wang, Timothy C.

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