Effects of Peroxisome Proliferator-Activated Receptor Ligand and Brown Seaweed Based Compound on Megakaryocyte

Abstract

Purpose The ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR)γ has been reported to promote the formation of platelets from megakaryocytes and accelerate platelet recovery. The endogenous prostaglandin 15-deoxy-Δ12,14 prostaglandin J2 (15d-PGJ2) is a ligand of PPARγ. Fucoidans are constituents of brown seaweed, and their anticoagulant and antithrombotic actions are recognized. In this study, we analyzed how PPAR ligand and brown seaweed based compound affect megakaryocyte and platelet in vitro. Methods Platelets were isolated from discarded plateletpheresis products by centrifugation. We used DAMI and Meg-01 cells as well. We treated these cells with 15d-PGJ2, GW9662, fucoidan, GW6471, and celecoxib. Then their effects on platelet membrane glycoproteins and PPARγ, PPARα and COX-2 expression, thrombogenicity and genetic regulation were analyzed. Results 15d-PGJ2 induced megakaryocytic differentiation evidence in morphology and flow cytometry analysis. In microarray analysis, fucoidan showed early growth response 1 (EGR1), Fc receptor, IgG, high affinity 1 (FCGR1), YME1 like 1 ATPase (YME1L1), stanniocalcin 1 (STC1) and cytochrome P450 family 11 subfamily B member 2 (CYP11B2) genes upregulation on megakaryocytes. Conclusion These findings support PPAR ligand, and brown seaweed based compound plays a role in megakaryocytic differentiation even in genomic level. Keywords: Megakaryocytes, Platelet, PPAR ligand, Fucoidan