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

被引:187
作者
Farrell, JJ
Taupin, D
Koh, TJ
Chen, D
Zhao, CM
Podolsky, DK
Wang, TC
机构
[1] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA
[2] Canberra Hosp, Gastroenterol Unit, Garran, Australia
[3] Norwegian Univ Sci & Technol, Univ Trondheim Hosp, N-7034 Trondheim, Norway
关键词
D O I
10.1172/JCI12529
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
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页码:193 / 204
页数:12
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