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


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.
Xu
Hong Yu
HY
Department of Gastroenterology, First Hospital, Harbin Medical University, China.
Li
Bao Jie
BJ
Wang
Rui Feng
RF
Andersson
Roland
R
D000818:Animals; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D006498:Hepatectomy; D022781:Hepatocytes / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000097:blood; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000096:biosynthesis*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D051881:Receptor, Notch1 / Q000096:biosynthesis*; D000072099:Serrate-Jagged Proteins; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; C000606275:Jag1 protein, rat; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497763:Notch1 protein, rat; D018809:Proliferating Cell Nuclear Antigen; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins; D014409:Tumor Necrosis Factor-alpha