Background & Aims
We previously reported that platelets promote hepatocyte proliferation. In this study,
we focused on the role of platelets in liver sinusoidal endothelial cells (LSECs)
in addition to their role in hepatocyte in liver regeneration.
Methods
Immortalized human LSECs (TMNK-1) were used. The LSECs were co-cultured with human
platelets, and the proliferation of LSECs and the excretion of growth factors and
interleukin-6 (IL-6) were subsequently measured. The main factor from platelets which
induced the excretion of IL-6 from LSECs was determined using inhibitors of each component
contained in the platelets. The need for direct contact between platelets and LSECs
was investigated using cell culture inserts. The proliferation of human primary hepatocytes
was measured after the addition of the supernatant of LSECs cultured with or without
platelets.
Results
The number of LSECs cocultured with platelets significantly increased. Excretion of
IL-6 and vascular endothelial growth factor (VEGF) increased in LSECs with platelets.
JTE-013, a specific antagonist for sphingosine 1-phosphate (S1P) 2 receptors, inhibited
the excretion of IL-6 from LSECs after the addition of platelets. When the platelets
and LSECs were separated by the cell culture insert, the excretion of IL-6 from LSECs
was decreased. DNA synthesis was significantly increased in human primary hepatocytes
cultured with the supernatant of LSECs with platelets.
Conclusions
Platelets promote LSEC proliferation and induce IL-6 and VEGF production. Direct contact
between the platelets and LSECs and S1P, that are contained in platelets, were involved
in the excretion of IL-6 from LSECs. IL-6 from LSECs induced proliferation of parenchymal
hepatocytes.
Abbreviations:
LSECs (liver sinusoidal endothelial cells), IL-6 (interleukin-6), VEGF (vascular endothelial growth factor), S1P (sphingosine 1-phosphate), HGF (hepatocyte growth factor), EGF (epidermal growth factor), PDGF (platelet-derived growth factor), STAT3 (signal transducer and activator of transcription 3), ERK1/2 (extracellular signal-regulated protein kinase 1/2), NO (nitric oxide), IGF-1 (insulin-like growth factor 1), I/R (ischemia/reperfusion), PRP (Platelet-rich plasma), ACD (acid citrate dextrose), HSA (human serum albumin), ANOVA (analysis of variance)Keywords
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Article info
Publication history
Published online: June 23, 2010
Accepted:
April 9,
2010
Received in revised form:
March 11,
2010
Received:
November 25,
2009
Identification
Copyright
© 2010 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
