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

Abstract

Objective: 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.

Material and methods: 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.

Results: 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.

Conclusions: 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.