Therapeutic effect of adenoviral-mediated hepatocyte growth factor gene administration on TNBS-induced colitis in mice.
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.
Mukoyama
Tomoyuki
T
Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Japan.
Kanbe
Takamasa
T
Murai
Rie
R
Murawaki
Yoshiyuki
Y
Shimomura
Takashi
T
Hashiguchi
Ko-Ichi
K
Saeki
Toshiya
T
Ichiba
Miho
M
Yoshida
Yoko
Y
Tanabe
Naotada
N
Kurimasa
Akihiro
A
Harada
Ken-Ichi
K
Yashima
Kazuo
K
Hisatome
Ichiro
I
Ito
Hisao
H
Murawaki
Yoshikazu
Y
Shiota
Goshi
G
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*
D017228:Hepatocyte Growth Factor; D014302:Trinitrobenzenesulfonic Acid