Platelets Promote Liver Regeneration in Early Period after Hepatectomy in Mice

Abstract

Platelets contain several growth factors, including platelet-derived growth factor and hepatocyte growth factor. We examined the effects of platelet increment on liver regeneration after 70% hepatectomy. Hepatectomies were carried out in male BALB/c mice, and subsequently divided into three groups: (i) untreated mice, (ii) thrombocytotic mice induced with thrombopoietin, and (iii) thrombocytopenic mice induced with anti-platelet antibody. Growth kinetics in the liver were analyzed as a function of the liver/body weight ratio, the mitotic index, the proliferating cell nuclear antigen labeling index and Ki-67 labeling index. Activation of signal transduction pathways relating to cell proliferation were examined, including the STAT3, Akt, and ERK1/2 pathways. Platelet accumulation in the residual liver was quantified by immunohistochemistry and transmission electron microscopy. In thrombocytotic and thrombocytopenic mice, liver/body weight ratios and Ki-67 labeling indices were significantly increased and significantly decreased, respectively, compared with untreated mice 48 hours post-hepatectomy. The Akt pathway was strongly activated, and platelet accumulation was significantly increased in thrombocytotic group 5 minutes post-hepatectomy compared with normal and thrombocytopenic groups. After hepatectomy platelets accumulated in the sinusoids of liver and promoted hepatocyte proliferation in early period after hepatectomy. By increasing or decreasing the platelet, marked changes in liver regeneration can occur, due to differences in cellular signaling and mitosis.