Transient von Willebrand factor-mediated platelet influx stimulates liver regeneration after partial hepatectomy in mice.
In addition to their function in thrombosis and haemostasis, platelets play an important role in the stimulation of liver regeneration. It has been suggested that platelets deliver mitogenic cargo to the regenerating liver, and accumulation of platelets in the regenerating liver has been demonstrated. We studied kinetics of platelet influx in the regenerating liver and investigated the signal that initiates platelet influx.



We visualized platelets in the liver remnant after partial hepatectomy in mice using intravital microscopy and assessed liver regeneration by examination of liver/body weight ratio and the number of proliferating hepatocytes examined by immunohistochemistry.



We demonstrated rapid but transient platelet influx into the liver remnant after a partial liver resection. Liver regeneration in thrombocytopenic mice was substantially impaired as evidenced by a reduced liver-to-body weight ratio and decreased numbers of proliferating hepatocytes at day 3 compared to mice with normal platelet counts. In contrast, liver regeneration was only mildly impaired when thrombocytopaenia was induced 2 hours after partial liver resection. Platelet influx into the liver remnant was virtually absent in the presence of an antibody to von Willebrand factor (VWF) suggesting that VWF release from liver sinusoidal endothelial cells mediates platelet influx. Additionally, liver regeneration in mice deficient in VWF was markedly impaired.



A rapid but transient VWF-dependent platelet influx into the liver remnant drives platelet-mediated liver regeneration.
Surgical Research Laboratory Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Marc
M
Kirschbaum
Calvin, Phoebe & Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada.
Craig N
CN
Jenne
Surgical Research Laboratory Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Zwanida J
ZJ
Veldhuis
Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Klaas A
KA
Sjollema
Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, 94276 Le Kremlin-Bicêtre, France.
Peter J
PJ
Lenting
Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Ben N G
BNG
Giepmans
Section of Hepatobiliairy Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Robert J
RJ
Porte
Calvin, Phoebe & Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada.
Paul
P
Kubes
Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, 94276 Le Kremlin-Bicêtre, France.
Cécile V
CV
Denis
Surgical Research Laboratory Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.|Section of Hepatobiliairy Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Ton
0000-0002-3503-7140
T
Lisman
D000818:Animals; D001792:Blood Platelets; D006487:Hemostasis; D006498:Hepatectomy; D008099:Liver / Q000502:physiology* / Q000601:surgery; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013927:Thrombosis / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism*
D014841:von Willebrand Factor
hepatectomy; liver regeneration; platelet; von Willebrand Factor