Hepatocyte growth factor gene therapy accelerates regeneration in cirrhotic mouse livers after hepatectomy.
BACKGROUND
Impaired regeneration and dysfunction of the cirrhotic liver following partial hepatectomy (PHx) are the most serious risk factors for postoperative liver failure.


OBJECTIVE
Using naked hepatocyte growth factor (HGF) plasmid by the electroporation (EP) in vivo method, we investigated HGF for its role and mechanism of proliferation and restoration of liver mass in cirrhotic mice following PHx.


METHODS
Eight week old female mice were used.


METHODS
HGF plasmid 50 micro g was injected intramuscularly and transferred by EP in vivo once a week for three weeks. After establishment of carbon tetrachloride induced cirrhosis, mice underwent PHx. The HGF treated group was given naked HGF plasmid four days before PHx, and additional HGF was given once a week until they were killed, while a control group was given only empty plasmid. Mice were killed 2, 4, 10, and 14 days after PHx. Morphological and functional restoration of the liver were examined, as well as activation of mitogen activated protein kinase (MAPK) and mRNA levels of HGF activator (HGFA).


RESULTS
The HGF treated group demonstrated a continuous threefold increase in HGF levels in plasma. Therapy with HGF in cirrhotic PHx resulted in effective liver regeneration via restoration of HGFA and activation of MAPK p44/p42, accelerated normalisation of liver function, and increased collagen degradation.


CONCLUSIONS
HGF gene therapy by in vivo EP may be useful for hepatic resection in cirrhotic livers by stimulating liver proliferative and collagenolytic capacities, as well as accelerating functional recovery.
Xue
F
F
Third Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Takahara
T
T
Yata
Y
Y
Kuwabara
Y
Y
Shinno
E
E
Nonome
K
K
Minemura
M
M
Takahara
S
S
Li
X
X
Yamato
E
E
Watanabe
A
A
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D018274:Electroporation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D017093:Liver Failure / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008115:Liver Regeneration / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects; D011183:Postoperative Complications / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*
D017228:Hepatocyte Growth Factor; D020928:Mitogen-Activated Protein Kinases