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Lycopene binding compromised PDGF-AA/-AB signaling and migration in smooth muscle cells and fibroblasts: prediction of the possible lycopene binding site within PDGF

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Abstract

Platelet-derived growth factor (PDGF) is a potent stimulator of growth and motility of smooth muscle cells (SMCs) and fibroblasts. Abnormalities of PDGF/PDGF receptor (PDGFR) are thought to contribute to vascular diseases and malignancy. We previously showed that natural carotenoid lycopene can directly bind to PDGF-BB and affect its related functions in vascular SMCs. In this study we examined lycopene effect on PDGF-AA/-AB-induced signaling and migration in SMCs and fibroblasts. We found that lycopene inhibited PDGF-AA-induced SMC and fibroblast migration in a concentration-dependent manner. Lycopene reduced PDGF-AA signaling, including phosphorylation in PDGFR-α and its downstream protein kinases/enzymes. It also inhibited PDGF-AB-induced signaling and cell migration. However, lycopene did not affect PDGF-induced reactive oxygen species production and H2O2-induced PDGFR phosphorylation. The binding analysis revealed that lycopene but not β-carotene could directly bind to PDGF-AA in vitro and in plasma and this binding competitively inhibited lycopene interaction with PDGF-BB, suggesting that lycopene bound to PDGF-AA/-BB at a homologous/similar region within PDGF. Moreover, the docking and binding analyses predicted that the lycopene-binding region within PDGF was located at loop 2 region. Taken together, we provide here evidence that lycopene interacts with PDGF-AA/-AB and compromises their intracellular signaling, leading to a marked inhibition on PDGF-AA/-AB-induced migration in both SMCs and fibroblasts. We also predicted its binding region within PDGF and proved its anti-vascular injury effect in vivo. The results, together with our previous findings, suggest lycopene special affinity/effect for PDGF family and its possible application in prevention in vascular diseases and malignancy.

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Abbreviations

ERK:

extracellular matrix-regulated kinase

PDGF:

platelet-derived growth factor

PDGFR-α:

PDGF receptor α

PLC-γ:

phospholipase C-γ

MAPK:

mitogen-activated protein kinase

SMC(s):

smooth muscle cell(s)

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Acknowledgments

We thanked Dr. Su-Jane Wang for providing us with rat aorta. The work was supported by the research grants from Changhua Christian Hospital, Shin Kong Wu Ho-Su Memorial Hospital, and the National Science Council.

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, Changhua Christian Hospital, Changhua, Taiwan

    Ching-Pei Chen

  2. School of Medicine, Fu-Jen Catholic University, No. 510, Chung-Cheng Road, Hsinchuang, Taipei, Taiwan

    Chi-Feng Hung, Shao-Chen Lee, Huey-Ming Lo, Pi-Hui Wu & Wen-Bin Wu

  3. Section of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

    Huey-Ming Lo

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  1. Ching-Pei Chen
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Correspondence to Wen-Bin Wu.

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Chen, CP., Hung, CF., Lee, SC. et al. Lycopene binding compromised PDGF-AA/-AB signaling and migration in smooth muscle cells and fibroblasts: prediction of the possible lycopene binding site within PDGF. Naunyn-Schmied Arch Pharmacol 381, 401–414 (2010). https://doi.org/10.1007/s00210-010-0501-1

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