Factor XIII improves gastric stress lesions in rats.
OBJECTIVE
Tissue transglutaminase has been reported to be involved in the healing of experimental gastric ulcer; nevertheless, other type(s) of transglutaminase could be involved. The present experiments aimed at examining whether plasma transglutaminase (factor XIIIa) contributes to such healing and at evaluating whether factor XIII supplementation improves gastric mucosal lesions.


METHODS
The healing effect of 200 U/kg of factor XIII administered intravenously was examined using a water immersion restraint rat model of stress gastric damage. The rats were sacrified 0, 2, 4, and 12 h after stress. The gastric mucosa was examined macroscopically and microscopically, and the transglutaminase activities were assayed in serum and gastric mucosa. Factor XIIIa and tissue transglutaminase protein levels in the gastric mucosa were analyzed by immunoblot. Immunohistochemistry was used to identify the location of tissue transglutaminase, factor XIIIa, and fibronectin in the gastric mucosa.


RESULTS
The transglutaminase activity, reduced by stress in the gastric mucosa, increased up to 12 h after stress, peaking at 4 h, when the ulcer index significantly decreased. The serum transglutaminase level was low at all time points. Exogenous administration of factor XIII allowed a faster reduction of the ulcer index that was coincident with an increased transglutaminase activity in the mucosa. Both tissue transglutaminase and factor XIIIa protein levels were reduced by 6 h of stress and increased after factor XIII administration. Immunohistochemistry showed a colocalization of both factor XIIIa and tissue transglutaminase with fibronectin in the extracellular matrix of the damaged area.


CONCLUSIONS
Two forms of transglutaminase are involved in the healing of stress-induced gastric erosions, and factor XIII administration allows faster gastric mucosa healing.
D'Argenio
G
G
Gastrointestinal Unit, School of Medicine, Federico II University, Naples, Italy. dargenio@unina.it
Iovino
P
P
Cosenza
V
V
Della Valle
N
N
De Ritis
F
F
Mazzacca
G
G
D000818:Animals; D001797:Blood Protein Electrophoresis; D015153:Blotting, Western; D005176:Factor XIII / Q000627:therapeutic use*; D005753:Gastric Mucosa / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D006654:Histology, Comparative; D007150:Immunohistochemistry; D008297:Male; D008853:Microscopy; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D013312:Stress, Physiological / Q000150:complications*; D011503:Transglutaminases / Q000187:drug effects / Q000378:metabolism
D005176:Factor XIII; D011503:Transglutaminases