title: Repeated enemas with hepatocyte growth factor selectively stimulate epithelial cell proliferation of injured mucosa in rats with experimental colitis.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: HGF Hepatic Regeneration Therapy Project, Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Setoyama
authors.forename: Akio
authors.initials: A
authors.lastname: Ido
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Numata
authors.forename: Akihiro
authors.initials: A
authors.lastname: Moriuchi
authors.forename: Naohisa
authors.initials: N
authors.lastname: Yamaji
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tamai
authors.forename: Keita
authors.initials: K
authors.lastname: Funakawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujita
authors.forename: Toshio
authors.initials: T
authors.lastname: Sakiyama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Uto
authors.forename: Makoto
authors.initials: M
authors.lastname: Oketani
authors.forename: Hirohito
authors.initials: H
authors.lastname: Tsubouchi
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage*; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
chemical_list: C066855:HGF protein, human; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate