Ten paths of PKA signaling pathway regulate hepatocyte proliferation in rat liver regeneration

Generally, protein kinase A (PKA) signaling pathway regulates many physiological activities such as cell proliferation and metabolism. However, little is known about how PKA signaling pathway composed of 16 paths participates in regulating hepatocyte proliferation during rat liver regeneration (LR). To explore the influence PKA signaling pathway upon hepatocytes at gene transcription level, Rat Genome 230 2.0 Array was used to detect expression changes of 225 related genes in isolated hepatocytes from rat regenerating livers, showing that 197 genes were contained in the array and 78 genes were significantly changed. Moreover, bioinformatics and systems biology methods were applied to analyze the precise role of PKA signaling pathway in regulating hepatocyte proliferation during LR, and it was found that 10 paths were related to hepatocyte proliferation during rat LR. In detail, 5 paths including SR→Gα-S→PKA, GPCR→Gα-S→PKA, GPCR→PLC→PKA, ET-1→PLC→PKA and hypoxia→AMP→PKA launched hepatocyte proliferation in initiating phase of LR, and then 3 paths including βR→Gα-S→PKA, GPCR→PLC→PKA and GPCR→Gβγ a"currency sign AcⅤ Ⅵ→PKA enhanced hepatocyte proliferation in progressing phase, whereas 3 paths including TGFB→SMAD3/4→PKA, CaCn→ACIX a"currency sign PKA, SST→Gα-Ⅰ a"currency sign PKA inhibited hepatocyte proliferation in terminating phase of LR. In conclusion, 78 genes and 10 paths of PKA signaling pathway regulate hepatocyte proliferation in rat LR.