PB0913 - Desialylated platelets are involved in the proliferation of HepG2 cells

Background: Platelets without sialic acid on the surface leads to their clearance from the circulation mediated by Ashwell-Morell receptor (AMR) on hepatocytes. On the other hand, desialylated platelets regulate the expression of TPO mRNA by promoting the activation of JAK2-STAT3. In the previous study, we demonstrated the possibility that the proliferation of HepG2 cells were accelerated by desialylated platelets. However, the mechanism by which desialylated platelets accelerate the proliferation of HepG2 cells remains unknown.

Aims: The aim of this study was to elucidate the mechanism for the regulation of desialylated platelets-mediated proliferation of HepG2 cells.

Methods: Freshly drawn whole blood from healthy volunteers was centrifuged to isolate platelet rich plasma (PRP), and then PRP were treated with neuraminidase. After the presence of terminal galactose residues was stained with FITC-Ricinus Communis agglutinin-1 (RCA-1), samples were analyzed by flow cytometer. The proliferation of HepG2 cell in the presence of desialylated platelets or platelets was evaluated by using WST-8 assay. The phosphorylation of JAK2, STAT3, p38 MAPK and ERK were detected by using Western blotting.

Results: The proliferation of HepG2 cells significantly increased by desialylated platelets in a time-dependent manner compared with platelets. To elucidate the mechanism of HepG2 cell proliferation, we analyzed the cell signaling pathway. Although the phospholylation of JAK2 and STAT3 were not detected by desialylated platelets or platelets, the phospholylation of ERK and p38 MAPK were augmented only by desialylated platelets. Furthermore, the proliferation of HepG2 cells in the presence of desialylated platelets were inhibited by MEK inhibitor (PD98059) or p38 MAPK inhibitor (SB203580).

Conclusion(s): Desialylated platelets regulates the proliferation of HepG2 cells by phosphorylating ERK and p38 MAPK.