title: Naked gene therapy of hepatocyte growth factor for dextran sulfate sodium-induced colitis in mice.
abstract: Ulcerative colitis (UC) is progressive and relapsing disease. To explore the therapeutic effects of naked gene therapy of hepatocyte growth factor (HGF) on UC, the SRalpha promoter driving HGF gene was intrarectally administered to the mice in which colitis was induced by dextran sulfate sodium (DSS). Expression of the transgene was seen in surface epithelium, lamina propria, and muscularis mucosae. The HGF-treated mice showed reduced colonic mucosal damage and increased body weights, compared with control mice (P < 0.01 and P < 0.05, respectively). The HGF-treated mice displayed increased number of PCNA-positive cells and decreased number of apoptotic cells than in control mice (P < 0.01, each). Phosphorylated AKT was dramatically increased after HGF gene administration, however, phosphorylated ERK1/2 was not altered. Microarray analysis revealed that HGF induced expression of proliferation- and apoptosis-associated genes. These data suggest that naked HGF gene delivery causes therapeutic effects through regulation of many downstream genes.
authors.affiliation: Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Kanbe
authors.forename: Rie
authors.initials: R
authors.lastname: Murai
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Mukoyama
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Murawaki
authors.forename: Ko-ichi
authors.initials: K
authors.lastname: Hashiguchi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuchiya
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: Eiji
authors.initials: E
authors.lastname: Nishimuki
authors.forename: Noriko
authors.initials: N
authors.lastname: Shabana
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Kishimoto
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kojyo
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Miura
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Murawaki
authors.forename: Hironaka
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Goshi
authors.initials: G
authors.lastname: Shiota
mesh_terms: D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D049109:Cell Proliferation; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000628:therapy*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015316:Genetic Therapy / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000502:physiology*; D015151:Immunoblotting; D051379:Mice; D008807:Mice, Inbred BALB C; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D017228:Hepatocyte Growth Factor; D016264:Dextran Sulfate; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3