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

作者：Kim Ki Young; Ahn Jin Hee; Cheon Hyae Gyeong^*

来源：Molecular and Cellular Biochemistry, 2011, 358(1-2): 375-385.

DOI：10.1007/s11010-011-0989-9

• Angiogenesis
• PPAR gamma
• VEGF
• PTEN
• HUVEC
• VEGFR-2

Peroxisome proliferator-activated receptor gamma (PPAR gamma) activation has anti-angiogenic and apoptotic effects in endothelial cells. Here, we investigated the mechanisms of the anti-angiogenic action of a novel PPAR gamma 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 (VEGF(165), 5 ng/ml). VEGF(165)-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 VEGF(165)-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 p85 alpha, 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 PPAR gamma antagonist. In summary, KR-62980 inhibited VEGF(165)-induced angiogenesis in HUVECs by PPAR gamma-mediated dual mechanisms: VEGFR-2 downregulation and PTEN upregulation.

• 出版日期2011-12