Changes in serum levels of growth factors in healthy individuals after living related liver donation.
ABSTRACT To obtain better insight into the kinetics of hepatic growth factors following partial hepatectomy for living related liver donation, we investigated the postoperative changes in serum levels of hepatocyte growth factor (HGF), epidermal growth factor (EGF), vascular epidermal growth factor (VEGF), and transforming growth factor-alpha (TGF-alpha).
Eighteen healthy donors undergoing right hepatectomy for living related donation were enrolled in this study. Serum levels of HGF, EGF, VEGF, and TGF-alpha were measured using enzyme-linked immunosorbent assay kits before surgery, at 2 hours after resection, and daily during 5 days postoperatively.
Mean preoperative HGF serum levels in healthy adults were 778 +/- 64 pg/mL. Within 2 hours after operation, they significantly increased to 9608 +/- 3111 pg/mL afterward decreasing to 2726 +/- 241 at day 1 and 2283 +/- 250 pg/mL at day 2. Hereafter HGF serum levels stabilized at increased levels until day 5 (2109 +/- 138, 2047 +/- 219, 2283 +/- 336 pg/mL, respectively). At all time points, the differences between pre- and postoperative HGF levels were significant (P < .01). In contrast, VEGF and EGF serum levels showed no significant differences between pre- and postoperative levels at all time points. TGF-alpha was not detected using a commercially available test with a detection limit of 10 ng/mL, suggesting only low TGF-alpha serum levels following liver resection.
Significantly increased HGF serum levels after hepatectomy demonstrate its crucial role among the other investigated growth factors in regeneration of the remnant liver tissue during the early period after the operation.
Article: Liver regeneration.[show abstract] [hide abstract]
ABSTRACT: The liver can precisely regulate its growth and mass. Surgical resection of hepatic lobes or hepatocyte loss caused by viral or chemical injury triggers hepatocyte replication while enlarged liver mass is corrected by apoptosis. Hepatocytes have a great replicative capacity and are capable of repopulating the liver. However, "stem-like" cells proliferate when hepatocyte replication is blocked or delayed. Detailed studies of the mechanisms that regulate liver growth have been done in animals subjected to partial hepatectomy or chemical injury. Substantial progress has been achieved using appropriate transgenic and knockout mouse models for this work. Gene expression in the regenerating liver can be divided into several phases, starting with expression of a large number of immediate early genes. Hepatocytes need to be primed before they can fully respond to the growth factors HGF (Hepatocyte Growth Factor), TGFalpha (Transforming Growth Factor Alpha), and EGF (Epidermal Growth Factor) in vitro. Priming requires the cytokines TNF and IL-6 in addition to other agents that prevent cytotoxicity. Reactive Oxygen Species and glutathione content can determine whether the TNF effect on hepatocytes is proliferative or apoptotic. At least four transcription factors, NFkappaB, STAT3 (which are strongly induced by TNF), AP-1 and C/EBPbeta play major roles in the initiation of liver regeneration. In addition, extensive remodeling of the hepatic extracellular matrix occurs shortly after partial hepatectomy. Progression through the cell cycle beyond the initiation phase requires growth factors. The expression of Cyclin D1 probably establishes the stage at which replication becomes growth factor-independent and autonomous. Knowledge about the mechanisms of liver regeneration can now be applied to correct clinical problems caused by deficient liver growth.Journal of Hepatology 02/2000; 32(1 Suppl):19-31. · 9.86 Impact Factor