Naked gene therapy of hepatocyte growth factor for dextran sulfate sodium-induced colitis in mice

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 SRα promoter driving HGF gene was intrarectally administered to the mice in which colitis was induced by dextran sulfate sodium (DSS). E...

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Veröffentlicht in:Biochemical and biophysical research communications 2006-07, Vol.345 (4), p.1517-1525
Hauptverfasser: Kanbe, Takamasa, Murai, Rie, Mukoyama, Tomoyuki, Murawaki, Yoshiyuki, Hashiguchi, Ko-ichi, Yoshida, Yoko, Tsuchiya, Hiroyuki, Kurimasa, Akihiro, Harada, Ken-ichi, Yashima, Kazuo, Nishimuki, Eiji, Shabana, Noriko, Kishimoto, Yukihiro, Kojyo, Haruhiko, Miura, Kunihiko, Murawaki, Yoshikazu, Kawasaki, Hironaka, Shiota, Goshi
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container_end_page 1525
container_issue 4
container_start_page 1517
container_title Biochemical and biophysical research communications
container_volume 345
creator Kanbe, Takamasa
Murai, Rie
Mukoyama, Tomoyuki
Murawaki, Yoshiyuki
Hashiguchi, Ko-ichi
Yoshida, Yoko
Tsuchiya, Hiroyuki
Kurimasa, Akihiro
Harada, Ken-ichi
Yashima, Kazuo
Nishimuki, Eiji
Shabana, Noriko
Kishimoto, Yukihiro
Kojyo, Haruhiko
Miura, Kunihiko
Murawaki, Yoshikazu
Kawasaki, Hironaka
Shiota, Goshi
description 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 SRα 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.
doi_str_mv 10.1016/j.bbrc.2006.05.084
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ispartof Biochemical and biophysical research communications, 2006-07, Vol.345 (4), p.1517-1525
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subjects 60 APPLIED LIFE SCIENCES
Animals
Apoptosis
Body Weight
CELL PROLIFERATION
Colitis - chemically induced
Colitis - genetics
Colitis - therapy
Colon - metabolism
Colon - pathology
DEXTRAN
Dextran Sulfate
DNA
EPITHELIUM
Female
Gene Expression
Gene Expression Profiling
GENE REGULATION
GENE THERAPY
GENES
Genetic Therapy - methods
GROWTH FACTORS
Hepatocyte growth factor
Hepatocyte Growth Factor - genetics
Hepatocyte Growth Factor - physiology
Immunoblotting
MICE
Mice, Inbred BALB C
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinase 3 - metabolism
Naked DNA
Oligonucleotide Array Sequence Analysis
Phosphorylation
Proto-Oncogene Proteins c-akt - metabolism
RECTAL ADMINISTRATION
SODIUM
SULFATES
Ulcerative colitis
URANIUM CARBIDES
title Naked gene therapy of hepatocyte growth factor for dextran sulfate sodium-induced colitis in mice
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