Differential expression of the genes involved in amino acids and nitrogen metabolisms during liver regeneration of mice

Liver regeneration is a highly coordinated response to hepatic injury or resection that is controlled by the body's overall requirement for liver function. The level of circulating amino acids in blood increases after acute liver injury and administration of amino acid mixtures induces hepatic DNA replication. These findings suggest a close connection between amino acid metabolism and hepatic proliferation. However, the underlying molecular mechanisms have not been completely elucidated. Here, we applied a cDNA micro-array technique to analyze expression profiles of the genes associated with nitrogen and amino acid metabolism during liver regeneration in mice following treatment with CCl4. Seventy-nine genes were identified for their significantly altered expression patterns at different stages of liver damage and regeneration. We observed that the numbers of down-regulated genes were remarkably higher than that of up-regulated genes at 1.5 days following carbon tetrachloride administration when hepatic DNA replication was most active, indicating the existence of a counter balance between cell proliferation and liver metabolism functions. Our results suggest that suppression of amino acids metabolism after acute liver injury results in the accumulation of amino acids in plasma that serves as a driving force for liver regeneration.