Factor XIII modulates intestinal epithelial wound healing in vitro.
BACKGROUND
An acquired deficiency of blood coagulation factor XIII has been proposed to cause an impairment of intestinal wound healing and hemostasis in patients with inflammatory bowel diseases. Substitution of factor XIII seems to result in a rapid improvement of intestinal wound healing. Our aim was therefore to characterize the role of factor XIII in the modulation of intestinal wound healing in vitro.


METHODS
Factor XIII was added to subconfluent cultures of two non-transformed small-intestinal epithelial cell lines (IEC-6, IEC-18) and three human colon cancer-derived epithelial cell lines (T84, CaCo-2, HT-29) with subsequent assessment of cell proliferation with a colorimetric 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenylformazan (MTT) assay. The effects on epithelial cell migration in vitro were assessed with an in vitro wounding model of confluent IEC-6 cell monolayers.


RESULTS
Factor XIII caused a modest inhibition of proliferation of IEC-6 and IEC-18 cells. However, factor XIII significantly stimulated proliferation of T84, CaCo-2. and HT-29 cell lines. In addition, thrombin-activated factor Xill promoted intestinal epithelial cell restitution in vitro on average 2.5-fold. The modulatory effects of factor XIII could not be significantly blocked by anti-transforming growth factor beta (TGFbeta).


CONCLUSIONS
Factor XIII may promote intestinal epithelial wound healing by enhancement of epithelial cell restitution through a TGFbeta-independent pathway. This may explain previously described beneficial effects of factor XIII in the treatment of active ulcerative colitis.
Cario
E
E
Dept. of Internal Medicine, University of Essen, Germany.
Goebell
H
H
Dignass
A U
AU
D000818:Animals; D002460:Cell Line; D005176:Factor XIII / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000503:physiopathology*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000502:physiology; D011503:Transglutaminases / Q000502:physiology; D014407:Tumor Cells, Cultured; D014945:Wound Healing / Q000502:physiology*
D016212:Transforming Growth Factor beta; D005176:Factor XIII; D011503:Transglutaminases