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- Title
Vascular endothelial growth factor suppresses TNFSF15 production in endothelial cells by stimulating miR-31 and miR-20a expression via activation of Akt and Erk signals.
- Authors
Deng, Hui-Ting; Liu, Hai-Lin; Zhai, Bei-Bei; Zhang, Kun; Xu, Guo-Ce; Peng, Xue-Mei; Zhang, Qiang-Zhe; Li, Lu-Yuan
- Abstract
Tumor necrosis factor superfamily-15 ( TNFSF15; VEGI; TL1A) is a negative modulator of angiogenesis for blood vessel homeostasis and is produced by endothelial cells in a mature vasculature. It is known to be downregulated by vascular endothelial growth factor ( VEGF), a major regulator of neovascularization but the mechanism of this interaction is unclear. Here we report that VEGF is able to stimulate the production of two micro RNAs, miR-20a and miR-31, which directly target the 3′- UTR of TNFSF15. Additionally, we show that two VEGF-stimulated cell growth signals, Erk and Akt, are responsible for promoting the expression of miR-20a and miR-31. Treatment of human umbilical vein endothelial cells ( HUVECs) with Akt inhibitor LY294002 results in diminished miR-20a and miR-31 production, while Erk inhibitor U0126 prevented VEGF-stimulated expression of miR-20a but not that of miR-31. Furthermore, inactivation of either Erk or Akt signals restores TNFSF15 gene expression. In an angiogenesis assay, elevated miR-20a or miR-31 levels in HUVECs leads to enhancement of capillary-like tubule formation in vitro, whereas lowered miR-20a and miR-31 levels results in an inhibition. These findings are consistent with the view that miR-20a and miR-31 mediate VEGF-induced downregulation of TNFSF15. Targeting these micro RNA molecules may therefore provide an effective approach to inhibit angiogenesis.
- Subjects
VASCULAR endothelial growth factors; TUMOR necrosis factors; NEOVASCULARIZATION; PROTEIN kinase B; ENDOTHELIAL cells; CELLULAR signal transduction
- Publication
FEBS Open Bio, 2017, Vol 7, Issue 1, p108
- ISSN
2211-5463
- Publication type
Article
- DOI
10.1002/2211-5463.12171