Activation of AP-1 Transcription Factors Differentiates FGF2 and Vascular Endothelial Growth Factor Regulation of Endothelial Nitric-oxide Synthase Expression in Placental Artery Endothelial Cells

Mata‐Greenwood, Eugenia; Liao, Wu-xiang; Wang, Wen; Zheng, Jing; Chen, Dong‐bao

doi:10.1074/jbc.m109.092791

Cited by 13 publications

(13 citation statements)

References 42 publications

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“…25,26 Upon bFGF treatment, which promotes endothelial cells activation, endothelial cells respond with the induction of αvβ3 complex and uPA but also with the activation of FOSL1. 9,27 Our results are compatible with a model in which FOSL1 functions as a modulator of both complexes to precisely tuning the level of key molecules on endothelial cell surface. FOSL1 can function as either an activator or a repressor, depending on the gene-context, controlling in this way the delicate equilibrium between adhesion and migration in sprouting angiogenesis.…”

Section: Role Of the Ap-1 Transcription Factor Fosl1 In Endothelial Csupporting

confidence: 91%

Role of the AP-1 transcription factor FOSL1 in endothelial cells adhesion and migration

Galvagni

Orlandini

Oliviero

2013

Cell Adhesion & Migration

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Vasculogenesis and angiogenesis, the fundamental processes by which new blood vessels are formed, involve the proliferation, migration, and remodeling of endothelial cells. Dynamic adhesion of endothelial cells to extracellular matrix plays a fundamental role in all these events. Key regulators of endothelial cells adhesion and migration are the αvβ3 and uPA-uPAR complexes. The αvβ3 integrin heterodimer is the receptor for extracellular matrix components such as vitronectin and is overexpressed on the cell surface of angiogenic endothelial cells, but not quiescent cells lining normal vessels. The uPA-uPAR complex contributes to extracellular matrix remodeling by mediating proteolytic activity at the leading edge of migrating cells. We recently reported that the FOSL1 transcription factor of the AP-1 family plays a pivotal role in the regulation of the level of the αvβ3 and uPA-uPAR complexes on the surface of endothelial cells. In this commentary, we review the current knowledge of αv and β3 transcriptional regulation in endothelial cells and discuss the role of FOSL1 in angiogenesis.

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Section: Role Of the Ap-1 Transcription Factor Fosl1 In Endothelial Csupporting

confidence: 91%

Role of the AP-1 transcription factor FOSL1 in endothelial cells adhesion and migration

Galvagni

Orlandini

Oliviero

2013

Cell Adhesion & Migration

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“…Western blotting was performed as previously described (Mata-Greenwood et al 2010). Briefly, protein extracts (30 µg) were prepared in a cold lysis buffer, heat denatured in a Laemmli buffer, separated on SDS-PAGE, and transferred to PVDF membranes.…”

Section: Methodsmentioning

confidence: 99%

“…GR promoters B, C, D, F, and H were cloned into the firefly luciferase-pGL3 reporter vectors (Promega), as previously described (Mata-Greenwood et al 2010). GR promoter regions were selected to include putative essential DNA elements such as initiator (Inr) and downstream promoters (DPE).…”

Section: Methodsmentioning

confidence: 99%

Endothelial glucocorticoid receptor promoter methylation according to dexamethasone sensitivity

Mata‐Greenwood

Jackson

Pearce

et al. 2015

Journal of Molecular Endocrinology

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We have previously shown that in vitro sensitivity to dexamethasone (DEX) stimulation in human endothelial cells is positively regulated by the glucocorticoid receptor (NR3C1, GR). The present study determined the role of differential GR transcriptional regulation in glucocorticoid sensitivity. We studied 25 human umbilical vein endothelial cells (HUVECs) that had been previously characterized as DEX-sensitive (n = 15), or resistant (n = 10). Real-time PCR analysis of GR 5′UTR mRNA isoforms showed that all HUVECs expressed isoforms 1B, 1C, 1D, 1F, and 1H, and isoforms 1B and 1C were predominantly expressed. DEX-resistant cells expressed higher basal levels of the 5′UTR mRNA isoforms 1C and 1D, but lower levels of the 5′UTR mRNA isoform 1F than DEX-sensitive cells. DEX treatment significantly decreased GRα and GR-1C mRNA isoform expression in DEX-resistant cells only. Reporter luciferase assays indicated that differential GR mRNA isoform expression was not due to differential promoter usage between DEX-sensitive and DEX-resistant cells. Analysis of promoter methylation, however, showed that DEX-sensitive cells have higher methylation levels of promoter 1D and lower methylation levels of promoter 1F than DEX-resistant cells. Treatment with 5-aza-2-deoxycytidine abolished the differential 5′UTR mRNA isoform expression between DEX-sensitive and DEX-resistant cells. Finally, both GRα overexpression and 5-aza-2-deoxycytidine treatment eliminated the differences between sensitivity groups to DEX-mediated downregulation of endothelial nitric oxide synthase (NOS3), and upregulation of plasminogen activator inhibitor 1 (SERPINE1). In sum, human endothelial GR 5′UTR mRNA expression is regulated by promoter methylation with DEX-sensitive and DEX-resistant cells having different GR promoter methylation patterns.

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“…One study has shown that VEGF potently induces c-fos mRNA expression but have moderate effect on c-jun mRNA levels in HUVEC (Armesilla et al, 1999). Another work indicated that VEGF weakly induces c-jun and JunB protein in placental artery endothelial cells (Mata-Greenwood et al, 2010). Nevertheless, surprisingly nothing is known whether these AP-1 family members play role in VEGF functions.…”

Section: Introductionmentioning

confidence: 99%

AP-1 transcription factor mediates VEGF-induced endothelial cell migration and proliferation

Jia

Cui

et al. 2016

Microvascular Research

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VEGF, upon binding to its endothelial cell specific receptors VEGF-R1 and VEGF-R2, can induce endothelial cell migration, proliferation and angiogenesis. However, the molecular mechanism of these effects still remains unclear. In this study, we investigated whether VEGF promotes human umbilical vascular endothelial cell (HUVEC) migration and proliferation through activator protein-1 transcription factor (AP-1) family. We first showed that VEGF induces immediate-early genes AP-1 family gene expression differentially with the profound induction of JunB (both mRNA and protein) under various conditions (PBS, DMSO or control adenoviruses). The increase in AP-1 mRNA expression occurs primarily at the transcriptional level. Inhibition of AP-1 DNA binding activity by adenovirus expressing a potent dominant negative form of c-Fos (Afos) significantly attenuated VEGF-induced HUVEC migration and proliferation and cyclin D1 expression. Knockdown of JunB with adenovirus expressing JunB shRNA reduces VEGF-induced JunB expression and attenuated HUVEC migration. However the shJunB-expressing virus has no effect on VEGF-induced cyclin D1 protein expression and proliferation. These results suggest that VEGF-induced endothelial migration is mediated primarily by induction of JunB whereas the promotion of endothelial proliferation by VEGF is mediated by JunB-independent AP-1 family members.

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Activation of AP-1 Transcription Factors Differentiates FGF2 and Vascular Endothelial Growth Factor Regulation of Endothelial Nitric-oxide Synthase Expression in Placental Artery Endothelial Cells

Cited by 13 publications

References 42 publications

Role of the AP-1 transcription factor FOSL1 in endothelial cells adhesion and migration

Role of the AP-1 transcription factor FOSL1 in endothelial cells adhesion and migration

Endothelial glucocorticoid receptor promoter methylation according to dexamethasone sensitivity

AP-1 transcription factor mediates VEGF-induced endothelial cell migration and proliferation

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