Table 1 Model variables and parameters and their approximate biological correlates

Name

Nominal or Starting Value

Approximate Biological Correlate

 M

20.8 (rat)

Relative nutrient and toxin delivery/absorption rate in the liver

 G

3.5x10⁻⁴ (rat)

Growth rate of hepatocyte mass [mass equivalent doublings/min]

 k_IL6

1.5

Rate at which non-parenchymal cells (primarily Kupffer cells) are able to modify the cytokine milieu post-PHx

 κ_IL6

0.9

Rate of cytokine degradation

 V_JAK

2x10⁴

Maximum JAK activation rate

 K_m ^JAK

10⁴

JAK Michaelis concentration

 κ_JAK

0.4

Rate of JAK degradation

 [STAT3]

2

Relative concentration of monomeric STAT3 in the liver

 V_STAT3

7.5x10²

Maximum STAT3 phosphorylation rate

 K_m ^STAT3

0.4

pSTAT3 Michaelis concentration

 κ_STAT3

0.1

Rate of pSTAT3 dephosphorylation

 V_SOCS3

2.4x10⁴

Maximum SOCS3 activation rate

 K_m ^SOCS3

7x10⁻⁴

SOCS3 Michaelis concentration

 κ_SOCS3

0.4

Rate of SOCS3 degradation

 K_I ^SOCS3

1.5x10⁻²

SOCS3 Inhibition effect on STAT3 phosphorylation

 V_IE

2.5x10²

Maximum IE gene activation rate

 K_m ^IE

18

IE gene Michaelis concentration

 κ_IE

5

Rate of IE gene degradation

 κ_DEG

7

Rate of ECM degradation by MMPs

 κ_ECM

33

Rate of constitutive ECM degradation

 k_GF

0.113

Rate at which non-parenchymal cells (primarily hepatic stellate cells) directly & indirectly produce growth factors post-PHx

 κ_GF

0.23

Rate of growth factor degradation

 k_up

6x10⁻²

Rate of growth factor absorption/binding to the ECM

 k_Q

7x10⁻³

Maximum rate of hepatocyte transition from Quiescence to Primed [cells/min]

 k_P

4.4x10⁻³

Maximum rate of hepatocyte transition from Primed to Replicating [cells/min]

 k_R

5.4x10⁻³

Maximum rate of hepatocyte transition from Replicating to Quiescence [cells/min]

 k_prol

2x10⁻²

Rate of hepatocyte progression through the cell cycle [doublings/min]

 k_req

0.1

Requiescence rate of Primed hepatocytes [cells/min]

 θ_req

8

None

 β_req

3

None

 k_ap

0.1

Apoptosis rate of damaged hepatocytes

 θ_ap

9x10⁻³

None

 β_ap

4.5x10⁻³

None

 k_MBF

1

Rate of release of matrix bound factors during ECM remodeling

 κ_MBF

1

Degradation rate of matrix bound factors once they are released from the ECM

Name

Nominal or Starting Value

Approximate Biological Correlate

 Q

1

Fraction of hepatocytes in the Quiescent state

 P

0

Fraction of hepatocytes in the Primed state

 R

0

Fraction of hepatocytes in the Replicating state

 [IL-6]

1

Cytokine microenvironment of the liver

 [JAK]

1

Relative levels of activated receptors for cytokine signals in hepatocytes

 [pSTAT3]

1

Relative levels of phosphorylated STAT-3 compared to monomeric STAT-3 or other downstream effectors of cytokine signaling (i.e. NF-κB)

 [SOCS3]

1

Relative levels of SOCS3 or other inhibitors of cytokine signaling

 [IE]

1

Relative levels of immediate early genes induced in hepatocytes (e.g. cFOS, cJUN, and AP-1)

 [GF]

1

Relative bioavailability of growth factors promoting hepatocyte proliferation

 [ECM]

1

Relative levels of extracellular matrix buildup of matrix composed of collagens inhibitory to regeneration

 [MBF_ECM]

50

Relative levels of matrix bound factors priming hepatocytes

 [MBF_Free]

0

Relative levels of free matrix bound factors that were initially bound by ECM