2000 Fiscal Year Final Research Report Summary
Effect of portal hypertention by HGF gene therapy for liver cirrhosis
| Project/Area Number |
11671197
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | First Department of Surgery, Hyogo College of Medicine |
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Principal Investigator |
TAKEUCHI Masaharu Hyogo College of Medicine, First Department of Surgery, Research Associate, 医学部, 助手 (00258162)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAI Oshiyuki Hyogo College of Medicine, First Department of Surgery, Assistant Professor, 医学部, 講師 (50198024)
OKAMOTO Eizo Hyogo College of Medicine, First Department of Surgery, Professor, 医学部, 教授 (50068425)
FUJIMOTO Jiro Hyogo College of Medicine, First Department of Surgery, Professor, 医学部, 教授 (90199373)
UEKI Takahiro Hyogo College of Medicine, First Department of Surgery, Research Associate, 医学部, 助手 (10309461)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Liver cirrhosis / gene therapy / hepatocyte growth factor / portal hypertension / gene injection via hepatic artery |
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| Research Abstract |
We performed gene therapy for liver cirrhosis. Liver cirrhosis was induced in rats and dogs by administrating dimethylnitrosamine (DIN) for 3 consecutive days a week. DMN is a hepatotoxic drug that causes liver cirrhosis. Hepatocyte death and parenchymal collapse occurred and fibrous component is evident by 4weeks. The naked HGF plasmid was injected into hepatic artery after cirrhosis has been established. Naked HGF plasmid does not contain any virus or lipid component. HGF showed maximum value from 7days to 14days after gene transfer. Azan-Mallory staining revealed that Regions of fibrosis markedly decreased and lobular architecture was well organized in HGF injected rats, but in MOCK rats, the formation of fibrous septa joining the central area and pseudolobule formation were evident. Photo-image analyzer measured the extent of fibrosis. Cirrhotic liver treated with HGF gene showed more than 50% less fibrosis than control cirrhotic liver. The proposed mechanism of therapeutic effect of HGF on liver cirrhosis is that HGF promotes MMPs producrtion and digests fiber tissue. We investigated expression of MMP-3 in the liver by Western blotting. The marked increase of this was observed in liver tissue of 7 days and 14 days after transfection of HGF gene. This therapeutic effect suppressed the portal pressure in HGF treated rats. HGF gene therapy improved the portal hypertension, Cirrhotic rat treated with HGF showed less portal pressure than MOCK transfected control cirrhotic rats.
The naked HGF gene transfer into liver can treat rat liver cirrhosis and may be eventually translated into a useful clinical regimen for the treatment of patients with liver cirrhosis.
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