A new role for NF-κB in angiogenesis inhibition

Tabruyn, Sébastien P.; Griffioen, Arjan W.

doi:10.1038/sj.cdd.4402156

Cited by 53 publications

(36 citation statements)

References 48 publications

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“…Glrx expression itself is induced by NF-B activity (50) and up-regulated by inflammation and diabetes (13), suggesting deleterious positive feedback of the Glrx-NF-B-Wnt5a pathway. In accordance with our data, inhibition of NF-B with mutant IkB␣ increased disorganized vasculature in ischemic mouse hind limb (51) and enhanced tumor growth (52), suggesting that tight regulation of NF-B is required to maintain normal vascularization (53).…”

Section: Discussionsupporting

confidence: 75%

Glutaredoxin-1 Up-regulation Induces Soluble Vascular Endothelial Growth Factor Receptor 1, Attenuating Post-ischemia Limb Revascularization

Murdoch

Shuler

Haeussler

et al. 2014

Journal of Biological Chemistry

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Background: Glutaredoxin-1 (Glrx) inhibits endothelial cell migration by reversing protein-glutathione adducts. Results: Revascularization after hind limb ischemia was inhibited in Glrx transgenic mice. Glrx overexpression increased soluble VEGF receptor 1 (sFlt) in endothelial cells via NF-B-dependent Wnt5a production. Conclusion: Glrx enhances Wnt5a-induced anti-angiogenic sFlt in endothelial cells. Significance: Up-regulated Glrx inhibits VEGF signaling by increased sFlt causing impaired vascularization.

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Section: Discussionsupporting

confidence: 75%

Glutaredoxin-1 Up-regulation Induces Soluble Vascular Endothelial Growth Factor Receptor 1, Attenuating Post-ischemia Limb Revascularization

Murdoch

Shuler

Haeussler

et al. 2014

Journal of Biological Chemistry

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“…For instance, in tumor angiogenesis and other angiogenesis-related pathologies, at first glance it seems beneficial to reduce sustenance of a proinflammatory loop mediated by active NFjB. However, it has recently been postulated that NFjB activation is required for the activity of diverse anti-angiogenic compounds, and hence should not be inhibited in endothelial cells [71].…”

Section: Discussionmentioning

confidence: 99%

Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1)

2008

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Sustained proinflammatory responses in rheumatoid arthritis, atherosclerosis, and diabetic retinopathy, as well as in cancer, are often associated with increased angiogenesis that contributes to tissue disruption and disease progression. High mobility group B1 (HMGB1) has been recognized as a proinflammatory cytokine and more recently, as a proangiogenic factor. HMGB1 can either be passively released from necrotic cells or actively secreted in response to angiogenic and inflammatory signals. HMGB1 itself may signal through the receptor for advanced glycation end products (RAGE), and via toll-like receptors, TLR2 and TLR4. Activation of these receptors results in the activation of NFkappaB, which induces the upregulation of leukocyte adhesion molecules and the production of proinflammatory cytokines and angiogenic factors in both hematopoietic and endothelial cells, thereby promoting inflammation. Interestingly, HMGB1 seems to be involved in a positive feedback mechanism, that may help to sustain inflammation and angiogenesis in several pathological conditions, thereby contributing to disease progression. Endothelial cells express HMGB1, as well as the receptors RAGE, TLR2, and TLR4, and in diverse pathologies HMGB1 and its receptors are overexpressed. Furthermore, HMGB1-induced signaling can activate NFkappaB, which can subsequently induce the expression of HMGB1 receptors. Thus, HMGB1 can mediate amplification of inflammation and angiogenesis through increased secretion of HMGB1 and increased expression of the receptors it can interact with. In this review, we discuss signaling cascades that HMGB1 can induce via TLRs and RAGE, as well as its contribution to pathologies involving endothelial cells.

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“…Endothelial cell migration is known to be critical for the maintenance of vessel integrity from restoration of wound healing [23,24]. However, it is not clear whether the NF-κB signalling pathway plays a positive or negative role in endothelial cell migration [19,20,22,[25][26][27]. Thus in the present study we explored the contribution of β 2 -GPI on NF-κB signalling and endothelial cell migration.…”

Section: Introductionmentioning

confidence: 94%

“…NF-κB activation has been connected with multiple aspects of biological functions, including inflammation, cell proliferation, migration and tumour angiogenesis [18][19][20]. The NF-κB signalling pathway also plays an essential role in endothelial cells under environmental stress [21,22].…”

Section: Introductionmentioning

confidence: 99%

β2-Glycoprotein I inhibits endothelial cell migration through the nuclear factor κB signalling pathway and endothelial nitric oxide synthase activation

Chiu¹,

Chiou

Chiang³

2012

Biochemical Journal

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β₂-GPI (β₂-glycoprotein I) is a plasma glycoprotein ascribed with an anti-angiogenic function; however, the biological role and molecular basis of its action in cell migration remain unknown. The aim of the present study was to assess the contribution of β₂-GPI to HAEC (human aortic endothelial cell) migration and the details of its underlying mechanism. Using wound healing and Boyden chamber assays, we found that β₂-GPI inhibited endothelial cell migration, which was restored by its neutralizing antibody. NF-κB (nuclear factor κB) inhibitors and lentiviral siRNA (small interfering RNA) silencing of NF-κB significantly attenuated the inhibitory effect of β₂-GPI on cell migration. Moreover, β₂-GPI was found to induce IκBα (inhibitor of NF-κB) phosphorylation and translocation of p65 and p50. We further demonstrated that mRNA and protein levels of eNOS [endothelial NO (nitric oxide) synthase] and NO production were all increased by β₂-GPI and these effects were remarkably inhibited by NF-κB inhibitors and siRNAs of p65 and p50. Furthermore, β₂-GPI-mediated inhibition of cell migration was reversed by eNOS inhibitors and eNOS siRNAs. The findings of the present study provide novel insight into the ability of β₂-GPI to inhibit endothelial cell migration predominantly through the NF-κB/eNOS/NO signalling pathway, which indicates a potential direction for clinical therapy in vascular diseases.

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A new role for NF-κB in angiogenesis inhibition

Cited by 53 publications

References 48 publications

Glutaredoxin-1 Up-regulation Induces Soluble Vascular Endothelial Growth Factor Receptor 1, Attenuating Post-ischemia Limb Revascularization

Glutaredoxin-1 Up-regulation Induces Soluble Vascular Endothelial Growth Factor Receptor 1, Attenuating Post-ischemia Limb Revascularization

Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1)

β2-Glycoprotein I inhibits endothelial cell migration through the nuclear factor κB signalling pathway and endothelial nitric oxide synthase activation

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