Platelet-activating factor receptor mediates oxidized low density lipoprotein-induced migration of bone marrow-derived mesenchymal stem cells.
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.


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.
Medical Research Center for Ischemic Tissue Regeneration, Medical Research Institute, School of Medicine, Pusan National University, Gyeongsangnam-do, Republic of Korea.
Sang Hun
SH
Shin
Hae Young
HY
Song
Min Young
MY
Kim
Eun Kyung
EK
Do
Koan Hoi
KH
Kim
Jae Ho
JH
Kim
D000873:Anthracenes / Q000494:pharmacology; D000077214:Becaplermin; D001854:Bone Marrow Cells / Q000166:cytology*; D002070:Butadienes / Q000494:pharmacology; D002465:Cell Movement; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D000873:Anthracenes; D002070:Butadienes; D007093:Imidazoles; D008077:Lipoproteins, LDL; D009570:Nitriles; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D010982:Platelet-Derived Growth Factor; D047428:Protein Kinase Inhibitors; D020574:Proto-Oncogene Proteins c-sis; D011725:Pyridines; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; C113580:U 0126; C099252:oxidized low density lipoprotein; C039351:platelet activating factor receptor; D000077214:Becaplermin; C432165:pyrazolanthrone; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole