Modulation by amino acids of the expression of factors produced by hepatic stellate cells : its implication in injured liver

富含蛋白质或氨基酸的饮食对肝硬化患者的具体益处的机制仍有待阐明。肝损伤患者理想的氨基酸配方尚不确定。除了为蛋白质合成提供底物外，已知氨基酸影响多种细胞类型中细胞功能的调节。肝星状细胞产生多种与细胞生长、蛋白质产生、脂质和葡萄糖代谢等相关的因子，如肝细胞生长因子（HGF）和胰岛素样生长因子1（IGF-1）。本研究的目的是探讨氨基酸对肝星状细胞产生的因子的贡献。在评估的20种氨基酸中，除了亮氨酸之外，用谷氨酰胺和脯氨酸处理还显着增加了大鼠肝星状细胞克隆培养基中的HGF水平。通过添加up，HGF水平以剂量依赖性方式增加。 关于我们 至100 mM和1 mM的谷氨酰胺和脯氨酸。亮氨酸处理肝星状细胞后，p70 S6激酶和4E结合蛋白1的磷酸化迅速上调，而谷氨酰胺或脯氨酸处理诱导p70 S6激酶和4E结合蛋白1的磷酸化较小或不可检测，表明这些氨基酸对HGF产生的刺激作用似乎不依赖于mTOR信号通路。当大鼠接受谷氨酰胺或脯氨酸的腹腔注射时，治疗后12小时的肝脏和循环HGF水平显著高于对照组大鼠。此外，亮氨酸治疗刺激IGF-1的生产肝星状细胞克隆。谷氨酰胺和脯氨酸，除了亮氨酸，刺激肝星状细胞产生HGF。刺激HGF产生的潜在机制可根据氨基酸而变化。此外，氨基酸可以诱导肝星状细胞产生IGF-1。少

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 … More 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