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.