Attenuation of mouse acute colitis by naked hepatocyte growth factor gene transfer into the liver.
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.


OBJECTIVE
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-gamma, IL18, and TNF-alpha 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.
Hanawa
Takayasu
T
Department of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata City, Niigata 951-8510, Japan.
Suzuki
Kenji
K
Kawauchi
Yusuke
Y
Takamura
Masaaki
M
Yoneyama
Hiroyuki
H
Han
Gi Dong
GD
Kawachi
Hiroshi
H
Shimizu
Fujio
F
Asakura
Hitoshi
H
Miyazaki
Jun-ichi
J
Maruyama
Hiroki
H
Aoyagi
Yutaka
Y
D000208:Acute Disease; D000818:Animals; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016264:Dextran Sulfate / Q000633:toxicity; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D020382:Interleukin-18 / Q000235:genetics; D007763:Lac Operon; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010957:Plasmids / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D020382:Interleukin-18; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D017228:Hepatocyte Growth Factor; D007371:Interferon-gamma; D016264:Dextran Sulfate