title: Therapeutic effect of adenoviral-mediated hepatocyte growth factor gene administration on TNBS-induced colitis in mice.
abstract: Inflammatory bowel disease is incurable and relapsing disease. In order to clarify the effect of HGF gene therapy for inflammatory bowel disease, the adenoviral-mediated HGF gene was intrarectally administered into TNBS-colitis-induced Balb/c mice. Adenoviral-mediated gene delivery targetted its expression mainly to intestinal epithelial cells. Mucosal damage of HGF-treated intestine was significantly improved, and compared with LacZ-treated and saline administered mice (P<0.05, each). The mice treated with intrarectal administration of pAxCAHGF showed an increased average of body weight in comparison with that of pAxCALacZ-treated and saline-treated mice (P<0.05, each). The PCNA-positive cells in pAxCALacZ-treated mice were 44.7+/-4.9%, 51.7+/-6.6%, and 53.9+/-4.5% at 10, 15, and 21 days after TNBS administration, however those in pAxCAHGF-treated mice were increased to 74.3+/-5.1%, 67.1+/-2.6%, and 69.2+/-4.6% (P<0.05, each). The TUNEL-positive cells in pAxCALacZ-treated mice were 13.3+/-5.2%, 11.5+/-2.1%, and 7.2+/-5.2%, respectively. However, those in pAxCAHGF-treated mice at 10, 15, and 21 days were significantly decreased to 5.4+/-1.8%, 3.8+/-1.3%, and 5.7+/-2.8% (P<0.05, respectively). Expression of ERK1/2 was stronger in pAxCAHGF mice than in pAxCALacZ. These data suggest that adenoviral-mediated HGF gene therapy via an intrarectal route is a promising therapy for inflammatory bowel disease.
authors.affiliation: Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Mukoyama
authors.forename: Takamasa
authors.initials: T
authors.lastname: Kanbe
authors.forename: Rie
authors.initials: R
authors.lastname: Murai
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Murawaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimomura
authors.forename: Ko-Ichi
authors.initials: K
authors.lastname: Hashiguchi
authors.forename: Toshiya
authors.initials: T
authors.lastname: Saeki
authors.forename: Miho
authors.initials: M
authors.lastname: Ichiba
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Naotada
authors.initials: N
authors.lastname: Tanabe
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kurimasa
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Harada
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yashima
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hisatome
authors.forename: Hisao
authors.initials: H
authors.lastname: Ito
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Murawaki
authors.forename: Goshi
authors.initials: G
authors.lastname: Shiota
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000285:Administration, Rectal; D000818:Animals; D017209:Apoptosis; D001835:Body Weight / Q000235:genetics; D049109:Cell Proliferation; D003092:Colitis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D014302:Trinitrobenzenesulfonic Acid / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D017228:Hepatocyte Growth Factor; D014302:Trinitrobenzenesulfonic Acid