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Anti-angiogenic action of PPARγ ligand in human umbilical vein endothelial cells is mediated by PTEN upregulation and VEGFR-2 downregulation

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Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) activation has anti-angiogenic and apoptotic effects in endothelial cells. Here, we investigated the mechanisms of the anti-angiogenic action of a novel PPARγ ligand, KR-62980. KR-62980 inhibited in vitro basal tube formation and in vivo neovascularization in mice induced by Matrigel containing vascular endothelial growth factor (VEGF165, 5 ng/ml). VEGF165-induced cell proliferation and chemotactic migration in human umbilical vein endothelial cells (HUVECs) were also suppressed by KR-62980, in a mechanism accompanied by apoptotic cell death. KR-62980 downregulated the VEGF165-induced VEGFR-2 expression but increased the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in parallel with reduced phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2), PI3K p85α, and p38 MAPK. The knockdown of PTEN expression abolished KR-62980-suppressed cell proliferation and angiogenesis. All of the effects of KR-62980 disappeared with pretreatment of bisphenol A diaglycidyl ether (BADGE), a PPARγ antagonist. In summary, KR-62980 inhibited VEGF165-induced angiogenesis in HUVECs by PPARγ-mediated dual mechanisms: VEGFR-2 downregulation and PTEN upregulation.

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Acknowledgments

This research was supported by the Center for Biological, Modulators of the 21st Century Frontier R&D Program, Ministry of Science and Technology, Korea.

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Authors and Affiliations

  1. Bio-Organic Science Division, Korea Research Institute of Chemical Technology, P.O. Box 107, Yuseong-gu, Daejeon, 305-600, Korea

    Ki Young Kim, Jin Hee Ahn & Hyae Gyeong Cheon

  2. Department of Pharmacology and Pharmaceutical Sciences, Gachon University of Medicine and Science, Yeonsu-3 Dong, Yeonsu-Gu, Incheon, 406-799, Korea

    Hyae Gyeong Cheon

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  1. Ki Young Kim
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Correspondence to Hyae Gyeong Cheon.

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Kim, K.Y., Ahn, J.H. & Cheon, H.G. Anti-angiogenic action of PPARγ ligand in human umbilical vein endothelial cells is mediated by PTEN upregulation and VEGFR-2 downregulation. Mol Cell Biochem 358, 375–385 (2011). https://doi.org/10.1007/s11010-011-0989-9

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  • DOI: https://doi.org/10.1007/s11010-011-0989-9

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