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In vivo action of trefoil factor 2 (TFF2) to speed gastric repair is independent of cyclooxygenase
  1. Lin Xue1,
  2. Eitaro Aihara1,
  3. Daniel K Podolsky2,
  4. Timothy C Wang3,
  5. Marshall H Montrose1
  1. 1Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio, USA
  2. 2University of Texas Southwestern Medical School, Dallas, Texas, USA
  3. 3Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York, USA
  1. Correspondence to Marshall Montrose, Department of Molecular & Cellular Physiology, University of Cincinnati, ML 0576, 231 Albert Sabin Way, Cincinnati OH 45267, USA; mhm{at}


Objective Trefoil factor (TFF) peptides are expressed in gastric tissues, where they are part of the epithelial defences. To complement previous in vitro work, the goal of the present study was to examine directly if TFF2 was essential for gastric restitution in vivo during the recovery from microscopic damage.

Design TFF2 mutant (KO) mice were examined to study the epithelial repair process in vivo after laser-induced photodamage (LPD). Using two-photon laser energy absorption (710 nm), LPD was imposed on an ∼3–5 cell region of surface epithelium in anaesthetised mouse stomach. Responses to damage were evaluated during confocal time-lapse microscopy; including area of damage and the extracellular pH adjacent to the damaged surface (Cl-NERF pH sensor).

Results In control (TFF2+/+ and TFF2+/–) mice, damaged cells were exfoliated and the damaged epithelium was repaired by indomethacin. The resting surface pH was similar between control and TFF2-KO animals, but the post-LPD alkalisation of surface pH observed in control mice (∆pH 0.3±0.05, n=21) was attenuated in the TFF2-KO stomach (∆pH −0.08±0.09, n=18). Recobinant rat TFF3 partially rescued the attenuated surface pH change in TFF2-KO stomach, in the presence or absence of indomethacin.

Conclusions In the gastric epithelium in vivo, TFFs promote epithelial restitution via a mechanism that does not require cyclooxygenase activation. A novel role for TFFs to affect gastric surface pH is observed.

  • Trefoil factor
  • mutant mouse
  • two-photon microscopy
  • photodamage
  • microlesion
  • extracellular pH
  • gastric mucosal defence
  • gastric wound repair
  • imaging
  • trefoil peptides

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  • Funding This study was supported by National Institutes of Health Grant DK54940 (to MHM).

  • Competing interests DKB holds equity in ‘The GI Company’ which has licensed rights to TFF3, and DKB is an inventor on patents relevant to trefoil factors. No other authors have competing interests relevant to the work in this manuscript.

  • Provenance and peer review Not commissioned; externally peer reviewed.