Repeated enemas with hepatocyte growth factor selectively stimulate epithelial cell proliferation of injured mucosa in rats with experimental colitis

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. (C) 2011 Elsevier Inc. All rights reserved.