After partial hepatectomy, hepatocyte number is reduced which increases
metabolic load (M/N). Increased metabolic load drives hepatocyte growth factor
(GF) and tumor necrosis factor (TNF) expression. TNF degrades the ECM through
matrix metalloproteases (MMPs). TNF also leads to the expression of IL-6, which
initiates Janus kinase (JAK) signaling by activating STAT3. STAT3 leads to
transcription of suppressor of cytokine signaling 3 (SOCS3), and
intermediate-early genes (IE) that cause the hepatocyte to shift into a primed
state. As regeneration progresses and hepatocyte numbers increase, TNF levels
decrease and the ECM reforms and takes up GF. This stops the primed to
replicating cell transition, and drives the replicating to quiescence cell
transition.