Fig. 1

Schematic representation of the changes occurring during liver regeneration following PHx. a Detailed schematic. (1) Following PHx, hepatocytes respond within 30 s of tissue damage. Early post-PHx, previous work has shown release of ATP, increases in WNT signaling, and ionic Calcium release from hepatocyte mitochondria. (2) These responses in hepatocytes are likely to be driven by an increase portal blood flow, an increase in portal pressure, and an increase in metabolic demand per cell (increased nutrient availability, increased toxin flux, and increased extra-hepatic signals including LPS). (3) Signals from the blood and from hepatocytes activate non-parenchymal cells to produce factors governing hepatocyte entry into the cell cycle (including priming). b Simplified schematic diagram. This schematic shows the relationships included in the computational model. Several important pathways are lumped or represented as physiological transitions rather than including truly mechanistic detail. This physiological approach allows for insight into control principles of regeneration governed by archetypal signaling pathways. The gray matrix-bound factor (MBF) signaling was added to the model to investigate the contribution to liver mass recovery of matrix-bound signaling, but because of a relatively small impact on the dynamic mass recovery was excluded from further analyses