RT Journal Article
SR Electronic
T1 Hepatocyte Growth Factor Facilitates Colonic Mucosal Repair in Experimental Ulcerative Colitis in Rats
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 146
OP 151
DO 10.1124/jpet.103.054106
VO 307
IS 1
A1 Yoshihiro Tahara
A1 Akio Ido
A1 Shojiro Yamamoto
A1 Yoshifumi Miyata
A1 Hirofumi Uto
A1 Takeshi Hori
A1 Katsuhiro Hayashi
A1 Hirohito Tsubouchi
YR 2003
UL http://jpet.aspetjournals.org/content/307/1/146.abstract
AB Hepatocyte growth factor (HGF) modulates intestinal epithelial cell proliferation and migration, serving as a critical regulator of intestinal wound healing. In this study, we examined the effect of administration of recombinant human HGF on colonic mucosal damage in vivo. Acute colitis was induced in rats by feeding with 5% dextran sulfate sodium (DSS) for 7 days, and colitis was subsequently maintained by feeding with 1% DSS. On the 5th day of DSS administration, osmotic pumps releasing recombinant human HGF (200 μg/day) were implanted into the peritoneum of the rats. Continuous intraperitoneal delivery of HGF led to both increased serum human HGF levels and c-Met tyrosine phosphorylation within the colonic mucosa. Compared with mock-treated rats, those administered human HGF showed a reduction in colitis-associated weight loss, large intestinal shortening, and improved colonic erosions. Enhanced epithelial regeneration and cellular proliferation were observed in rats treated with recombinant human HGF. The weights of the liver, kidneys, and spleen were not affected by HGF administration. These results indicate that HGF administration accelerates colonic mucosal repair in rats with DSS-induced colitis and suggest that recombinant human HGF may be a useful therapeutic tool to facilitate intestinal wound healing in patients with ulcerative colitis. The American Society for Pharmacology and Experimental Therapeutics