Abstract：
AIMS:Hepatocyte growth factor (HGF) modulates intestinal epithelial cell proliferation and migration. We previously reported that systemic administration of recombinant human HGF (rh-HGF) ameliorated experimental colitis. However, an increase in serum HGF concentrations may induce undesired systemic effects, limiting the use of rh-HGF. To avoid possible side effects, we investigated the safety and efficacy of rectally administered rh-HGF as a treatment for experimental colitis. MAIN METHODS:We measured serum human HGF concentration following a single rectal enema of rh-HGF. Rats with 2,4,6-trinitrobenzene sulfonic acid (TNBS)- or dextran sulfate sodium (DSS)-induced colitis were treated with rectal enemas of rh-HGF once a day for seven days. The degree of mucosal injuries and the proliferative activity of the colon epithelium were examined. KEY FINDINGS:Rats administered a rectal enema of rh-HGF at a dose of 0.1 mg/ml or less had no detectable rh-HGF in the serum. Repeated enemas of rh-HGF at this dose significantly reduced mucosal injuries, both with respect to lesion size and inflammatory cell infiltration. This regimen also stimulated proliferation of epithelial cells surrounding injured mucosa; however, the cell proliferation of uninjured mucosa was not affected by this local treatment. SIGNIFICANCE:Rectally administered rh-HGF selectively accelerates the repair of injured mucosa in rat experimental colitis without systemic exposure to HGF. Rectal enemas of HGF are thus a potential novel and safe therapy for IBD.
journal_name
Life Scijournal_title
Life sciencesauthors
Setoyama H,Ido A,Numata M,Moriuchi A,Yamaji N,Tamai T,Funakawa K,Fujita H,Sakiyama T,Uto H,Oketani M,Tsubouchi Hdoi
10.1016/j.lfs.2011.06.019subject
Has Abstractpub_date
2011-08-15 00:00:00pages
269-75issue
7-8eissn
0024-3205issn
1879-0631pii
S0024-3205(11)00311-0journal_volume
89pub_type
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