In vivo action of trefoil factor 2 (TFF2) to speed gastric repair is independent of cyclooxygenase.
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.


METHODS
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 approximately 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 + or - 0.05, n=21) was attenuated in the TFF2-KO stomach (pH -0.08 + or - 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.
Xue
Lin
L
Department of Molecular & Cellular Physiology, University of Cincinnati, ML 0576, 231 Albert Sabin Way, Cincinnati OH 45267, USA.
Aihara
Eitaro
E
Podolsky
Daniel K
DK
Wang
Timothy C
TC
Montrose
Marshall H
MH
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000187:drug effects / Q000293:injuries / Q000378:metabolism / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009077:Mucins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010455:Peptides / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D000071164:Trefoil Factor-2; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
D016861:Cyclooxygenase Inhibitors; D009077:Mucins; D009124:Muscle Proteins; D010455:Peptides; C481546:TFF2 protein, mouse; C000604008:Tff2 protein, rat; D000071164:Trefoil Factor-2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin