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Oxidized phosphatidylcholine induces migration of bone marrow-derived mesenchymal stem cells through Krüppel-like factor 4-dependent mechanism

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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.

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Abbreviations

LDL:

Low density lipoprotein

PAF:

Platelet-activating factor

PGPC:

1-Palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine

POVPC:

1-Palmitoyl-2-oxovaleroyl-sn-glycero-3-phosphorylcholine

PAF-R:

PAF receptor

VSMCs:

Vascular smooth muscle cells

MSCs:

Mesenchymal stem cells

hBMSCs:

Human bone marrow-derived MSCs

RT-PCR:

Reverse transcription-polymerase chain reaction

siRNA:

Small interfering RNA

PDGF-BB:

Platelet-derived growth factor-BB

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Acknowledgments

This research was supported by a program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0020274) and by the MRC program (2010-0001251).

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Authors and Affiliations

  1. Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Gyeongsangnam-do, Yangsan, 626-870, Republic of Korea

    Sang Hun Shin, Hae Young Song, Min Young Kim, Eun Kyung Do & Jae Ho Kim

  2. Department of Physiology, School of Medicine, Pusan National University, Gyeongsangnam-do, Yangsan, 626-870, Republic of Korea

    Sang Hun Shin, Hae Young Song, Min Young Kim, Eun Kyung Do & Jae Ho Kim

  3. Department of Orthopaedic Surgery, School of Medicine, Pusan National University, Busan, 602-739, Republic of Korea

    Jung Sub Lee

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  1. Sang Hun Shin
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Correspondence to Jae Ho Kim.

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Shin, S.H., Song, H.Y., Kim, M.Y. et al. Oxidized phosphatidylcholine induces migration of bone marrow-derived mesenchymal stem cells through Krüppel-like factor 4-dependent mechanism. Mol Cell Biochem 352, 109–115 (2011). https://doi.org/10.1007/s11010-011-0745-1

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