論文 - 詳細
| RRC ID | 2278 |
|---|---|
| 著者 | Ozawa S, Uchiyama K, Nakamori M, Ueda K, Iwahashi M, Ueno H, Muragaki Y, Ooshima A, Yamaue H. |
| タイトル | Combination gene therapy of HGF and truncated type II TGF-beta receptor for rat liver cirrhosis after partial hepatectomy. |
| ジャーナル | Surgery |
| Abstract |
BACKGROUND:In a cirrhotic liver, the regenerative ability and specific functions are impaired; a hepatic resection increases the possibility of postoperative liver failure. Hepatocyte growth factor (HGF) stimulates liver regeneration, accelerates restoration of hepatic function, and improves fibrosis. A truncated type II transforming growth factor-beta receptor (TbetaTR), which specifically inhibits TGF-beta signaling as a dominant-negative receptor, appears to prevent the progression of liver fibrosis. We demonstrated the therapeutic efficacy of adenovirus-mediated HGF and TbetaTR gene transduction after partial hepatectomy for liver cirrhosis. METHODS:Rats were treated with dimethylnitrosamine for 3 weeks, and they all had severe cirrhosis. After partial hepatectomy (10%), we injected adenovirus expressing bacterial beta-galactosidase (AdLacZ), adenovirus expressing a truncated type II TGF-beta receptor (AdTbetaTR), adenovirus expressing hepatocyte growth factor (AdHGF), or AdTbetaTR + AdHGF into the portal vein, which was followed by an additional 2-week dimethylnitrosamine treatment. RESULTS:On histologic examination, fibrotic tissue had decreased in the livers of the AdTbetaTR + AdHGF-treated rats compared with rats that were treated by AdLacZ, AdTbetaTR alone, and AdHGF alone. Liver function, which included serum levels of alanine aminotransferase, improved significantly in AdTbetaTR + AdHGF-treated rats compared with all other groups. The number of hepatocytes that were positive for proliferating-cell nuclear antigen was greater (P < .05) in AdHGF alone and AdTbetaTR + AdHGF-treated rat livers than in AdLacZ- and AdTbetaTR-treated rats. All AdTbetaTR + AdHGF-treated rats survived >60 days, and AdTbetaTR + AdHGF treatment markedly improved the survival rate after a partial hepatectomy. CONCLUSION:Our results suggest that the combination of HGF and TbetaTR gene therapy may increase the possibility of hepatectomy in a cirrhotic liver by improving fibrosis, hepatic function, and hepatocyte regeneration. |
| 巻・号 | 139(4) |
| ページ | 563-73 |
| 公開日 | 2006-4-1 |
| DOI | 10.1016/j.surg.2005.10.003 |
| PII | S0039-6060(05)00647-1 |
| PMID | 16627068 |
| MeSH | Adenoviridae / genetics Animals Combined Modality Therapy Dimethylnitrosamine Disease Models, Animal Genetic Therapy / methods* Genetic Vectors Hepatectomy Hepatocyte Growth Factor / genetics* Humans Liver Cirrhosis, Experimental / surgery Liver Cirrhosis, Experimental / therapy* Protein Serine-Threonine Kinases Rats Receptor, Transforming Growth Factor-beta Type II Receptors, Transforming Growth Factor beta / genetics* |
| IF | 3.356 |
| 引用数 | 22 |
| WOS 分野 | SURGERY |
| リソース情報 | |
| 遺伝子材料 | AxCA rat HGF (RDB1553) |