Alterations of Notch/Jagged mRNA and protein expression after partial hepatectomy in rats

To investigate alterations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, the Notch/Jagged signaling pathway, and hepatocyte proliferation, and their correlation in rats subjected to partial hepatectomy.

Blood and liver tissues were sampled immediately (0), 5, 15, 30, 60, 180, 360, and 720 min, and 1, 2, 4, and 7 days after partial (70%) hepatectomy to measure plasma levels of TNF-alpha and IL-6, the expression of proliferating cell nuclear antigen (PCNA), Notch-1 and Jagged-1 protein, and mRNA in liver tissue.

Systemic levels of IL-6 significantly correlated with the expression of PCNA in hepatocytes (p<0.05) after partial (70%) hepatectomy. The increased expression of Notch-1 protein was located in the sinusoidal endothelium, while Jagged-1 protein was predominantly located in bile duct cells. Expression of both proteins was increased around the portal vein. mRNA expression of Notch-1 decreased between 6 h and 2 days after partial hepatectomy, while Jagged-1 increased between 3 and 6 h, decreased between 12 h and 2 days, and normalized on day 4 after hepatectomy.

Partial hepatectomy-induced hepatocyte proliferation was accompanied by an increase in systemic levels of IL-6, a pro-inflammatory response that plays a part in the proliferative process. The Notch/Jagged signaling pathways are activated and probably represent important contributors to the regenerative process following hepatectomy including both hepatocyte proliferation and bile duct formation and growth.