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.

Activation of protease-activated receptor (PAR) 1 by frog trefoil factor (TFF) 2 and PAR4 by human TFF2

“…The normal physiological levels of TFF2 could locally reach 10 lM in the gastric lumen [35]. TFF2-deficient mice were more susceptible to gastric ulceration than the normal controls [36]. We speculate that the expression of TFF2 and PAR4 in gastric mucosa and their interaction play an important role in mucosal healing and tissue homeostasis.…”

The trefoil factor family – small peptides with multiple functionalities

“…Mice lacking TFF2 exhibited minor gastric abnormalities, and in contrast to the TFF1 KO these mice had decreased thickness of the gastric mucosa. Furthermore, the mice had increased amounts of gastric acid, and exposure to indomethacin resulted in more severe gastric ulcerations than in wild type mice [155]. Microarray analysis of GI tissues from TFF2 KO mice showed that the majority of the most differentially expressed genes belonged to the immune system, e.g.…”

Genetic ablation of carbonic anhydrase IX disrupts gastric barrier function via claudin‐18 downregulation and acid backflux

“…Comparison of the gastric morphology and cellular composition of Car9 −/− and WT littermates was made at corresponding distances from the forestomach. Quantification of total cells and cell subtypes per gastric gland were determined as described before 54. For electron microscopy, samples of the corpus region were rapidly immersed in a fixative solution of 2.5% glutaraldehyde and 1.5% formaldehyde in HEPES buffer, pH 7.3, post‐fixed in OsO 4 and prepared for electron microscopy using a standard protocol 15…”