title: Oxidized phosphatidylcholine induces migration of bone marrow-derived mesenchymal stem cells through Krüppel-like factor 4-dependent mechanism.
abstract: Platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) and PAF-like oxidized phospholipids including 1-palmitoyl-2-oxovaleroyl-sn-glycero-3-phosphorylcholine (POVPC) are generated upon LDL oxidation. The aim of this study was to evaluate the question of whether POVPC can regulate migration of human bone marrow-derived stem cells (hBMSCs) and to characterize signaling mechanisms involved in the POVPC-induced cell migration. POVPC treatment resulted in dose- and time-dependent increase of hBMSCs migration. Treatment of cells with BN52021, a specific antagonist of PAF receptor, completely blocked cell migration induced by not only PAF but also POVPC. Silencing of endogenous PAF receptor expression using PAF receptor-specific small interfering RNA resulted in significant attenuation of cell migration induced by PAF or POVPC. Both PAF and POVPC induced expression of Krüppel-like factor 4 (KLF4) in hBMSCs. POVPC- or PAF-induced cell migration was abrogated by small interfering RNA-mediated depletion of endogenous KLF4. These results suggest that PAF receptor plays a pivotal role in POVPC-induced migration of human BMSCs through PAF receptor-mediated expression of KLF4.
authors.affiliation: Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Gyeongsangnam-do, Yangsan, Republic of Korea.
authors.forename: Sang Hun
authors.initials: SH
authors.lastname: Shin
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Song
authors.forename: Min Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Do
authors.forename: Jung Sub
authors.initials: JS
authors.lastname: Lee
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Kim
mesh_terms: D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D017931:DNA Primers; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000502:physiology*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D010713:Phosphatidylcholines; D034741:RNA, Small Interfering