| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,700,000 (Direct Cost: ¥1,700,000)
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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
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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 : 1136-1142,1995). Then, we investigated whether the intravenous administration of follistatin effectively promoted liver regeneration after partial hepatectomy. Autoradiography of the liver obtained 24 hours of infusion revealed that numerous grains were located in the parenchymal cells. Radioactivity of ^<125>I-follistatin in the liver remained elevated until 72 hours and declined markedly thereafter. When a booster shot of ^<125>I-follistatin was administered at 72 hours, radioactivity in the liver at 120 hours was markedly increased compared with that in rats received a single shot of ^<125>I-follistatin. After 120 hours of hepatectomy of 70%, remnant liver weight, liver regeneration rate, and DNA content were significantly higher in rats that received a booster shot of follistatin at 72 hours than those in control rats. The results indicate that follistatin administered intravenously accumulated in the liver and promotes liver regeneration after partial hepatectomy. These were reported in Hepatology (vol : 24 : 361-366,1996) Less
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