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Attenuation of mouse acute colitis by naked hepatocyte growth factor gene transfer into the liver
Author(s) -
Hanawa Takayasu,
Suzuki Kenji,
Kawauchi Yusuke,
Takamura Masaaki,
Yoneyama Hiroyuki,
Han Gi Dong,
Kawachi Hiroshi,
Shimizu Fujio,
Asakura Hitoshi,
Miyazaki Junichi,
Maruyama Hiroki,
Aoyagi Yutaka
Publication year - 2006
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.880
Subject(s) - hepatocyte growth factor , colitis , gene expression , genetic enhancement , hepatocyte , tumor necrosis factor alpha , inflammation , immunology , microbiology and biotechnology , cancer research , pharmacology , chemistry , medicine , gene , biology , in vitro , biochemistry , receptor
Abstract Background Hepatocyte growth factor (HGF) has multiple biological effects on a wide variety of cells. It modulates intestinal epithelial proliferation and migration, and critically regulates intestinal wound healing. Aims To investigate the therapeutic effect of HGF gene transfer, we introduced the HGF gene into the liver of mice with acute colitis. Methods The rat HGF expression plasmid vector, pCAGGS‐HGF, was injected via the tail vein into C57BL/6 mice, followed by dosing with dextran sulfate sodium in distilled water. Firstly, the HGF gene was injected once on day 0. Secondly, the HGF gene was injected on day 0 and again on day 2. Results Injection of the HGF gene ameliorated colitis with inhibition of both loss of body weight and shortening of colon length. It protected the colon from epithelial erosions and cellular infiltration. Expression of mRNAs for IFN‐γ, IL18, and TNF‐α was reduced in the colon. In contrast, expression of mRNA for IL‐10 was increased. The numbers of BrdU‐positive intestinal epithelial cells were increased, and the numbers of TUNEL‐positive apoptotic cells were decreased. Furthermore, a second injection prolonged the elevation of serum HGF levels, and ameliorated the symptoms better than a single injection. The empty pCAGGS plasmid did not ameliorate acute colitis. Conclusions HGF gene transfer attenuated acute colitis by facilitating intestinal wound repair as well as inhibiting inflammation, suggesting a new strategy for treatment of IBD. Copyright © 2006 John Wiley & Sons, Ltd.