Hepatocyte growth factor facilitates the repair of large colonic ulcers in 2,4,6-trinitrobenzene sulfonic acid-induced colitis in rats.
BACKGROUND
Hepatocyte growth factor (HGF) modulates intestinal epithelial cell proliferation and migration, serving as a critical regulator of intestinal wound healing. The aim of this study was to clarify the effects of administration of recombinant human HGF on colonic mucosal damage in vivo.


METHODS
Rats were given 7.5 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS) per rectum on day 0. On day 5, the degree of TNBS-induced colitis was evaluated endoscopically, and rats suffering from large ulcers (occupying more than two thirds of the luminal circumference) were treated with intravenous bolus injections of recombinant human HGF (1.0 mg/kg per day) or phosphate-buffered saline (PBS) for 5 days.


RESULTS
Rats with TNBS-induced colitis given human HGF showed a significant reduction in colonic ulcer coverage and large intestinal shortening compared with those treated with PBS. Administration of recombinant human HGF also stimulated the proliferation of epithelial cells and reduced the inflammatory cell infiltrate. Finally, HGF treatment decreased the myeloperoxidase activity and tumor necrosis factor alpha levels in the TNBS-inflamed colon tissues.


CONCLUSIONS
These results indicate that intravenous injection of HGF accelerates colonic mucosal repair and reduces infiltration of inflammatory cells in rats with TNBS-induced colitis and suggest that HGF has the potential to be a new therapeutic modality to promote intestinal mucosal repair in patients with inflammatory bowel disease.
Numata
Masatsugu
M
Department of Internal Medicine II, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki, Japan.
Ido
Akio
A
Moriuchi
Akihiro
A
Kim
Ildeok
I
Tahara
Yoshihiro
Y
Yamamoto
Shojiro
S
Hasuike
Satoru
S
Nagata
Kenji
K
Miyata
Yoshifumi
Y
Uto
Hirofumi
H
Tsubouchi
Hirohito
H
D000818:Animals; D049109:Cell Proliferation; D003108:Colonic Diseases / Q000188:drug therapy* / Q000503:physiopathology* / Q000662:veterinary; D017228:Hepatocyte Growth Factor / Q000494:pharmacology* / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D014302:Trinitrobenzenesulfonic Acid / Q000008:administration & dosage / Q000633:toxicity; D014456:Ulcer / Q000188:drug therapy* / Q000503:physiopathology* / Q000662:veterinary; D014945:Wound Healing
D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D014302:Trinitrobenzenesulfonic Acid