Effects of 15d-PGJ(2) on VEGF-induced angiogenic activities and expression of VEGF receptors in endothelial cells.

Prostaglandins & Other Lipid Mediators
Philip FunovicsAlicja Jozkowicz

Abstract

15-Deoxy-Delta(12,14)-prostaglandin-J(2) (15d-PGJ(2)) upregulates expression of vascular endothelial growth factor (VEGF), but may inhibit angiogenesis. We found that 15d-PGJ(2) (1-10muM) attenuated all VEGF-induced angiogenic activities in human umbilical vein endothelial cells (HUVEC). It blocked almost completely cell proliferation, potently reduced migration, assembly into tube-like network on matrigel, and growth of capillaries into collagen gel. 15d-PGJ(2) inhibited expression of VEGFR-1 and VEGFR-2 receptors both at mRNA and protein levels. This inhibition, however, was transient (observed after 6-12h, but not after 24h) and weak (20-30%), and could not fully explain inhibition of response to VEGF. Accordingly, proliferation was inhibited when 15d-PGJ(2) was added 24h after VEGF or in cells stimulated with basic fibroblast growth factor. Interestingly, 15d-PGJ(2) decreased activities of c-jun and c-myc in HUVEC and overexpression of c-myc attenuated its antiproliferative effects. This suggests that inhibition of this transcription factor by 15d-PGJ(2) contributes to decrease in angiogenic response.

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Citations

Mar 20, 2012·Trends in Molecular Medicine·M Dolores SalvadoJuan Miguel Redondo
Nov 27, 2014·Neoplasia : an International Journal for Oncology Research·Armin WiegeringChristoph Otto
Jun 16, 2010·Brazilian Journal of Biology = Revista Brasleira De Biologia·J E F Pereira LopesL F Gomes
Mar 29, 2019·Expert Opinion on Therapeutic Targets·Yuanyuan Cheng, Jianhui Rong
Jan 6, 2017·Journal of Diabetes Research·Jerzy Kotlinowski, Alicja Jozkowicz
Jul 28, 2020·Prostaglandins, Leukotrienes, and Essential Fatty Acids·Youjia DuPeter Zahradka
Jun 19, 2021·The Journal of Steroid Biochemistry and Molecular Biology·Juanru ChengYanfei Deng
Aug 3, 2021·Frontiers in Physiology·Bohae Rachel LeeNeelam Sharma-Walia

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