A focus on the role of platelets in liver regeneration: Do platelet-endothelial cell interactions initiate the regenerative process?

Abstract

Platelets are involved in the early phases of liver regeneration. Moreover, platelet transfusion and thrombocytosis were recently shown to enhance hepatocyte proliferation. However, the precise mechanisms remain elusive. This review discusses the latest updates regarding the mechanisms by which platelets stimulate liver regeneration, focusing on their interactions with liver sinusoidal endothelial cells and on their fate within the liver. Following liver injury, platelets are recruited to and trapped within the liver, where they adhere to the endothelium. Subsequent platelet activation results in the release of platelet granules, which stimulate hepatocyte proliferation through activation of the Akt and ERK1/2 signalling pathways. Platelets activate liver sinusoidal endothelial cells, leading to the secretion of growth factors, such as interleukin-6. Finally, liver sinusoidal cells and hepatocytes can also internalize platelets, but the effects of this alternate process on liver regeneration remain to be explored. A better understanding of the mechanisms by which platelets stimulate liver regeneration could lead to improvement in post-operative organ function and allow hepatectomies of a greater extent to be performed.

Keywords: Akt; ERK1/2; Endothelium; Hepatocyte; Interleukin-6; Internalization; Lipopolysaccharide; Liver sinusoidal endothelial cell; Macrophage-1 antigen; Proliferation; Signaling pathway; β2-integrin.