Hepatocyte growth factor facilitates colonic mucosal repair in experimental ulcerative colitis in rats.
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 microg/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.
Tahara
Yoshihiro
Y
Department of Internal Medicine II, Miyazaki Medical College, Kiyotake, Japan.
Ido
Akio
A
Yamamoto
Shojiro
S
Miyata
Yoshifumi
Y
Uto
Hirofumi
H
Hori
Takeshi
T
Hayashi
Katsuhiro
K
Tsubouchi
Hirohito
H
D000818:Animals; D003093:Colitis, Ulcerative / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D007263:Infusions, Parenteral; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000097:blood / Q000627:therapeutic use; D013154:Spleen / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects
D011994:Recombinant Proteins; D014443:Tyrosine; D017228:Hepatocyte Growth Factor; D016264:Dextran Sulfate; D019859:Proto-Oncogene Proteins c-met