| Budget Amount *help |
¥3,810,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Research Abstract |
The mechanisms involved in the specific benefits of protein-or amino acid-enriched diet in patients with liver cirrhosis remain to be elucidated. The ideal formula of amino acids in patients with liver injury is still uncertain. In addition to providing substrates for protein synthesis, amino acids are known to influence the regulation of cellular functions in a variety of cell types. Hepatic stellate cells produce a variety of factors associated with cell growth, protein production, lipid and glucose metabolism and so on such as hepatocyte growth factor (HGF) and insulin-like growth factor 1 (IGF-1). The aim of this study is to investigate the contribution of amino acids on the factors produced by hepatic stellate cells. Among 20 amino acids evaluated, treatment with glutamine and proline, in addition to leucine, significantly increased HGF levels in the culture medium of a rat hepatic stellate cell clone. The HGF levels were increased in a dose-dependent manner by the addition of up
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to 100 mM and 1 mM of glutamine and proline, respectively. While phosphorylation of p70 S6 kinase and 4E-binding protein 1 was rapidly up-regulated after leucine treatment in hepatic stellate cell done, treatment of glutamine or proline induced minor or undetectable phosphorylation of p70 S6 kinase and 4E binding protein 1, suggesting that the stimulatory effect of these amino acids on HGF production seems not to be dependent on mTOR signaling pathway. When rats received an intraperitoneal injection of glutamine or proline, hepatic and circulating HGF levels at 12 hours after treatment were significantly higher than in control rats. Furthermore, leucine treatment stimulated IGF-1 production by hepatic stellate cell clone. Glutamine and proline, in addition to leucine, stimulate HGF production by hepatic stellate cells. The mechanism underlying the stimulation of HGF production may vary depending on the amino acids. In addition, amino acids can induce IGF-1 production by hepatic stellate cells. Less
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