A simplified view of the impact of hepatocyte calcium signals during liver regeneration. After PH or toxic liver injury, a number of calcium mobilizing agonists are released inside or outside the liver, interacting with hepatocytes through autocrine, paracrine, and endocrine pathways. Diverse membrane receptors, either G protein coupled receptors (GPCR), tyrosine kinase receptors (TKR), or receptor channels (e.g., ionotropic purinergic receptors), can be involved in the generation of cytosolic calcium signals. These calcium movements in the cytosol can be transferred to other crucial compartments like the mitochondrion (Mito) or the nucleus, in which they could regulate respectively apoptosis and gene transcription. Previous studies have shown that cytosolic calcium signals regulate cell cycle progression from G0 to G1 and from G1 to S phases in hepatocytes after PH, at least in part through an impact on immediate early genes transcription, cyclin expression, and ERK and CREB phosphorylation.
