| Project/Area Number |
08557076
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Digestive surgery
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| Research Institution | Gunma University School of Medicine |
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Principal Investigator |
KOGURE Kimitaka Gunma University School of Medicine, Assistant Professor, 医学部, 講師 (80143220)
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| Co-Investigator(Kenkyū-buntansha) |
KANZAKI Makoto Institute for Molecular and Cellular Regulation Gunma University, Department of, 生体調節研究所, 助手 (10272262)
SHIBATA Hiroshi Institute for Molecular and Cellular Regulation Gunma University, Department of, 生体調節研究所, 助教授 (20235584)
KOJIMA Itaru Institute for Molecular and Cellular Regulation Gunma Uiversity, Department of C, 生体調節研究所, 教授 (60143492)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥15,600,000 (Direct Cost: ¥15,600,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥13,300,000 (Direct Cost: ¥13,300,000)
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| Keywords | follistatin / activin A, / liver regeneration / hepatectomy / analog of follistatin / 90%肝切除 |
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| Research Abstract |
Augmentation of liver regeneration, with an artificial support to maintain liver function necessary for survival, would be beneficial for the treatment of fulminant hepatic failure caused by viral infection and hepatic toxins. As well, massive hepatectomy to resect liver tumors can be performed safely if the growth of the remnant liver is promoted effectively. Recently, the roles of various growth factors in the regulation of hepatocyte growth have been elucidated. Activin A which belongs to the transforming growth factor beta super gene family is a potent autocrine growth inhibitor in hepatocytes. Activin A is induced in vivo after partial hepatectomy. Low levels of the messenger RNA for the betaA-subunit of activin are markedly increased 20 hours after hepatectomy. When follistatin, which binds activin and blocks its action, is infused into the portal vein immediately after hepatectomy of 70%, DNA is synthesized several hours earlier than in control rats and liver regeneration is sig
… More
nificantly augmented. Follistatin provides a potential therapeutic approach to promoting liver regeneration because it specifically blocks autocrine growth inhibitor. The results were reported in Gastroenterology (vol 108 : 1136-1142,1195). Then, we obtained the results that the intravenous administration of follistatin effectively promoted liver regeneration after partial hepatectomy. These were reported in Hepatology (vol : 24 : 361-366,1996). We then investigated the effects of follistation on liver regeneration under more critical condition, 90% hepatectomy in rats and obtained the results that follistatin was quite effective in promothing liver regeneration. In this project we made four kinds of analog follistatin to select the amino acid sequence which were expected to express the effects of follistatin (1.heparin binding side, 2.3.follistatin module, 4.c-terminal), and made two types of follistatin which were constructed with 288 and 315 of amino acids. We are investigating the effects of these analog follistatins on liver regeneration. Less
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