Keratinocyte growth factor ameliorates mucosal injury in an experimental model of colitis in rats.
OBJECTIVE
Keratinocyte growth factor (KGF) is known to enhance tissue repair in the skin; however, its role in the gastrointestinal tract is largely unknown. The aim of this study was to evaluate the effects of exogenous KGF in an experimental model of colitis in rats.


METHODS
KGF was administered before or after induction of colitis with 2,4,6-trinitrobenzenesulfonic acid/ethanol. In the first two study groups, KGF (5 mg/kg) was administered intraperitoneally 24 hours and 1 hour before induction of colitis; animals were killed 8 hours (n=10) and 1 week (n=10) after injury. In subsequent study groups, KGF or vehicle treatment was begun 24 hours after the induction of colitis at doses of 5 (n=20), 1 (n=10), and 0.1 (n=10) mg/kg intraperitoneally and continued once daily for 1 week. Colonic tissue samples were evaluated macroscopically and microscopically for mucosal injury and assayed for myeloperoxidase activity.


RESULTS
Administration of KGF after but not before induction of colitis significantly ameliorated tissue damage. Macroscopic necrosis and microscopic ulcerations were reduced by 40%-50% at KGF doses of 1 and 5 mg/kg.


CONCLUSIONS
Exogenous KGF has a key role in mucosal healing in an experimental model of colitis in rats.
Zeeh
J M
JM
Inflammatory Bowel Disease Center, Division of Gastroenterology, Harbor-UCLA Medical Center, Torrance, California, USA.
Procaccino
F
F
Hoffmann
P
P
Aukerman
S L
SL
McRoberts
J A
JA
Soltani
S
S
Pierce
G F
GF
Lakshmanan
J
J
Lacey
D
D
Eysselein
V E
VE
D000818:Animals; D002455:Cell Division; D003092:Colitis / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009077:Mucins / Q000378:metabolism; D009093:Mucus / Q000378:metabolism; D009336:Necrosis; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D014456:Ulcer / Q000473:pathology
C496455:Fgf7 protein, rat; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D009077:Mucins; D011994:Recombinant Proteins; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D009195:Peroxidase