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

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

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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Absence of expression of TFF2 mRNA and peptide in TFF2-deficient mice. (...
Absence of expression of TFF2 mRNA and peptide in TFF2-deficient mice. (a) Northern blot analysis of stomach RNA (top; 20 μg RNA per lane) using a mouse TFF2 exon 2 probe. TFF2-deficient mice (–/–) have no expression of TFF2 mRNA compared with heterozygous mice (+/–) or wild-type mice (+/+). Western blot analysis of stomach protein (bottom; 50 μg total protein per lane) using an Ab to human TFF2. TFF2-deficient mice have no expression of TFF2 protein compared with heterozygous mice or wild-type mice. Purified human TFF2 was used as a positive control (not shown). (b) Northern blot analysis of stomach RNA (20 μg RNA per lane) using a mouse TFF1 probe. Northern blot analysis was performed on gastrin deficient (–/–) and wild-type mice (+/+) as described in Methods. Twenty micrograms of RNA was loaded per lane. The blot was probed with an mTFF1 cDNA probe. The blot was then stripped and reprobed with a GAPDH cDNA probe. The TFF2-deficient mice (–/–) (lanes 4–6) have no increased expression of TFF1 mRNA compared with wild-type mice (+/+) (lanes 1–3) when controlled for GAPDH expression.