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TNFSF15 suppresses VEGF production in endothelial cells by stimulating miR-29b expression via activation of JNK-GATA3 signals

Vascular endothelial cell growth factor (VEGF) plays a pivotal role in promoting neovascularization. VEGF gene expression in vascular endothelial cells in normal tissues is maintained at low levels but becomes highly up-regulated in a variety of disease settings including cancers. Tumor necrosis fac...

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Autores principales: Zhang, Kun, Cai, Hong-Xing, Gao, Shan, Yang, Gui-Li, Deng, Hui-Ting, Xu, Guo-Ce, Han, Jihong, Zhang, Qiang-Zhe, Li, Lu-Yuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342489/
https://www.ncbi.nlm.nih.gov/pubmed/27589684
http://dx.doi.org/10.18632/oncotarget.11683
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author Zhang, Kun
Cai, Hong-Xing
Gao, Shan
Yang, Gui-Li
Deng, Hui-Ting
Xu, Guo-Ce
Han, Jihong
Zhang, Qiang-Zhe
Li, Lu-Yuan
author_facet Zhang, Kun
Cai, Hong-Xing
Gao, Shan
Yang, Gui-Li
Deng, Hui-Ting
Xu, Guo-Ce
Han, Jihong
Zhang, Qiang-Zhe
Li, Lu-Yuan
author_sort Zhang, Kun
collection PubMed
description Vascular endothelial cell growth factor (VEGF) plays a pivotal role in promoting neovascularization. VEGF gene expression in vascular endothelial cells in normal tissues is maintained at low levels but becomes highly up-regulated in a variety of disease settings including cancers. Tumor necrosis factor superfamily 15 (TNFSF15; VEGI; TL1A) is an anti-angiogenic cytokine prominently produced by endothelial cells in a normal vasculature. We report here that VEGF production in mouse endothelial cell line bEnd.3 can be inhibited by TNFSF15 via microRNA-29b (miR-29b) that targets the 3'-UTR of VEGF transcript. Blocking TNFSF15 activity by using either siRNA against the TNFSF15 receptor known as death domain-containing receptor-3 (DR3; TNFRSF25), or a neutralizing antibody 4-3H against TNFSF15, led to inhibition of miR-29b expression and reinvigoration of VEGF production. In addition, we found that TNFSF15 activated the JNK signaling pathway as well as the transcription factor GATA3, resulting in enhanced miR-29b production. Treatment of the cells either with SP600125, an inhibitor of JNK, or with JNK siRNA, led to eradication of TNFSF15-induced GATA3 expression. Moreover, GATA3 siRNA suppressed TNFSF15-induced miR-29b expression. These findings suggest that VEGF gene expression can be suppressed by TNFSF15-stimulated activation of the JNK-GATA3 signaling pathway which gives rise to up-regulation of miR-29b.
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spelling pubmed-53424892017-03-24 TNFSF15 suppresses VEGF production in endothelial cells by stimulating miR-29b expression via activation of JNK-GATA3 signals Zhang, Kun Cai, Hong-Xing Gao, Shan Yang, Gui-Li Deng, Hui-Ting Xu, Guo-Ce Han, Jihong Zhang, Qiang-Zhe Li, Lu-Yuan Oncotarget Research Paper Vascular endothelial cell growth factor (VEGF) plays a pivotal role in promoting neovascularization. VEGF gene expression in vascular endothelial cells in normal tissues is maintained at low levels but becomes highly up-regulated in a variety of disease settings including cancers. Tumor necrosis factor superfamily 15 (TNFSF15; VEGI; TL1A) is an anti-angiogenic cytokine prominently produced by endothelial cells in a normal vasculature. We report here that VEGF production in mouse endothelial cell line bEnd.3 can be inhibited by TNFSF15 via microRNA-29b (miR-29b) that targets the 3'-UTR of VEGF transcript. Blocking TNFSF15 activity by using either siRNA against the TNFSF15 receptor known as death domain-containing receptor-3 (DR3; TNFRSF25), or a neutralizing antibody 4-3H against TNFSF15, led to inhibition of miR-29b expression and reinvigoration of VEGF production. In addition, we found that TNFSF15 activated the JNK signaling pathway as well as the transcription factor GATA3, resulting in enhanced miR-29b production. Treatment of the cells either with SP600125, an inhibitor of JNK, or with JNK siRNA, led to eradication of TNFSF15-induced GATA3 expression. Moreover, GATA3 siRNA suppressed TNFSF15-induced miR-29b expression. These findings suggest that VEGF gene expression can be suppressed by TNFSF15-stimulated activation of the JNK-GATA3 signaling pathway which gives rise to up-regulation of miR-29b. Impact Journals LLC 2016-08-29 /pmc/articles/PMC5342489/ /pubmed/27589684 http://dx.doi.org/10.18632/oncotarget.11683 Text en Copyright: © 2016 Zhang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zhang, Kun
Cai, Hong-Xing
Gao, Shan
Yang, Gui-Li
Deng, Hui-Ting
Xu, Guo-Ce
Han, Jihong
Zhang, Qiang-Zhe
Li, Lu-Yuan
TNFSF15 suppresses VEGF production in endothelial cells by stimulating miR-29b expression via activation of JNK-GATA3 signals
title TNFSF15 suppresses VEGF production in endothelial cells by stimulating miR-29b expression via activation of JNK-GATA3 signals
title_full TNFSF15 suppresses VEGF production in endothelial cells by stimulating miR-29b expression via activation of JNK-GATA3 signals
title_fullStr TNFSF15 suppresses VEGF production in endothelial cells by stimulating miR-29b expression via activation of JNK-GATA3 signals
title_full_unstemmed TNFSF15 suppresses VEGF production in endothelial cells by stimulating miR-29b expression via activation of JNK-GATA3 signals
title_short TNFSF15 suppresses VEGF production in endothelial cells by stimulating miR-29b expression via activation of JNK-GATA3 signals
title_sort tnfsf15 suppresses vegf production in endothelial cells by stimulating mir-29b expression via activation of jnk-gata3 signals
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342489/
https://www.ncbi.nlm.nih.gov/pubmed/27589684
http://dx.doi.org/10.18632/oncotarget.11683
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