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  • Title: Platelet-activating factor receptor mediates oxidized low density lipoprotein-induced migration of bone marrow-derived mesenchymal stem cells.
    Author: Shin SH, Song HY, Kim MY, Do EK, Kim KH, Kim JH.
    Journal: Cell Physiol Biochem; 2010; 26(4-5):689-98. PubMed ID: 21063106.
    Abstract:
    BACKGROUND: Oxidized low density lipoprotein (oxLDL) is involved in the development of vascular diseases. Platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glyero-3-phosphorylcholine) is a key component of oxLDL. METHODS: In the present study, we evaluate whether oxLDL can regulate migration of human bone-marrow derived stem cells (hBMSCs) and characterize the role of PAF in the oxLDL-induced migration. RESULTS AND CONCLUSIONS: oxLDL stimulated chemotaxis of hBMSCs in vitro. Treatment of the cells with BN52021, a specific antagonist of PAF receptor (PAF-R), completely blocked the cell migration induced by PAF, but not platelet-derived growth factor (PDGF-BB). Using PAF-R-specific small interfering RNA, it was demonstrated that silencing of endogenous PAF-R expression significantly attenuated cell migration induced by PAF, but not PDGF-BB, suggesting the specific involvement of PAF-R in the oxLDL-induced cell migration. In addition, PAF-induced migration of hBMSCs was abrogated by pretreating cells with mitogen-activated protein kinase (MAPK) inhibitors, including the MEK inhibitor U0126, the p38 MAPK inhibitor SB202190, and the JNK inhibitor SP600125. Moreover, adenoviral overexpression of a dominant negative mutant of p38 MAPK blocked PAF-stimulated migration. Taken together, these results suggest that PAF plays a pivotal role in the oxLDL-induced recruitment of hBMSCs through mechanisms involving PAF-R-dependent activation of MAPKs.
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