The nexus between VEGF and NFκB orchestrates a hypoxia-independent neovasculogenesis.
Nuclear Factor-Kappa B [NFκB] activation triggers the elevation of various pro-angiogenic factors that contribute to the development and progression of diabetic vasculopathies. It has been demonstrated that vascular endothelial growth factor [VEGF] activates NFκB signaling pathway. Under the ischemi...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23533599/pdf/?tool=EBI |
| _version_ | 1818426554275856384 |
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| author | Michael DeNiro Falah H Al-Mohanna Osama Alsmadi Futwan A Al-Mohanna |
| author_facet | Michael DeNiro Falah H Al-Mohanna Osama Alsmadi Futwan A Al-Mohanna |
| author_sort | Michael DeNiro |
| collection | DOAJ |
| description | Nuclear Factor-Kappa B [NFκB] activation triggers the elevation of various pro-angiogenic factors that contribute to the development and progression of diabetic vasculopathies. It has been demonstrated that vascular endothelial growth factor [VEGF] activates NFκB signaling pathway. Under the ischemic microenvironments, hypoxia-inducible factor-1 [HIF-1] upregulates the expression of several proangiogenic mediators, which play crucial roles in ocular pathologies. Whereas YC-1, a soluble guanylyl cyclase [sGC] agonist, inhibits HIF-1 and NFκB signaling pathways in various cell and animal models. Throughout this investigation, we examined the molecular link between VEGF and NFκB under a hypoxia-independent microenvironment in human retinal microvascular endothelial cells [hRMVECs]. Our data indicate that VEGF promoted retinal neovasculogenesis via NFκB activation, enhancement of its DNA-binding activity, and upregulating NFκB/p65, SDF-1, CXCR4, FAK, αVβ3, α5β1, EPO, ET-1, and MMP-9 expression. Conversely, YC-1 impaired the activation of NFκB and its downstream signaling pathways, via attenuating IκB kinase phosphorylation, degradation and activation, and thus suppressing p65 phosphorylation, nuclear translocation, and inhibiting NFκB-DNA binding activity. We report for the first time that the nexus between VEGF and NFκB is implicated in coordinating a scheme that upregulates several pro-angiogenic molecules, which promotes retinal neovasculogenesis. Our data may suggest the potential use of YC-1 to attenuate the deleterious effects that are associated with hypoxia/ischemia-independent retinal vasculopathies. |
| first_indexed | 2024-12-14T14:31:41Z |
| format | Article |
| id | doaj.art-51432994845043539c9c6a992d49fb9c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T14:31:41Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-51432994845043539c9c6a992d49fb9c2022-12-21T22:57:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5902110.1371/journal.pone.0059021The nexus between VEGF and NFκB orchestrates a hypoxia-independent neovasculogenesis.Michael DeNiroFalah H Al-MohannaOsama AlsmadiFutwan A Al-MohannaNuclear Factor-Kappa B [NFκB] activation triggers the elevation of various pro-angiogenic factors that contribute to the development and progression of diabetic vasculopathies. It has been demonstrated that vascular endothelial growth factor [VEGF] activates NFκB signaling pathway. Under the ischemic microenvironments, hypoxia-inducible factor-1 [HIF-1] upregulates the expression of several proangiogenic mediators, which play crucial roles in ocular pathologies. Whereas YC-1, a soluble guanylyl cyclase [sGC] agonist, inhibits HIF-1 and NFκB signaling pathways in various cell and animal models. Throughout this investigation, we examined the molecular link between VEGF and NFκB under a hypoxia-independent microenvironment in human retinal microvascular endothelial cells [hRMVECs]. Our data indicate that VEGF promoted retinal neovasculogenesis via NFκB activation, enhancement of its DNA-binding activity, and upregulating NFκB/p65, SDF-1, CXCR4, FAK, αVβ3, α5β1, EPO, ET-1, and MMP-9 expression. Conversely, YC-1 impaired the activation of NFκB and its downstream signaling pathways, via attenuating IκB kinase phosphorylation, degradation and activation, and thus suppressing p65 phosphorylation, nuclear translocation, and inhibiting NFκB-DNA binding activity. We report for the first time that the nexus between VEGF and NFκB is implicated in coordinating a scheme that upregulates several pro-angiogenic molecules, which promotes retinal neovasculogenesis. Our data may suggest the potential use of YC-1 to attenuate the deleterious effects that are associated with hypoxia/ischemia-independent retinal vasculopathies.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23533599/pdf/?tool=EBI |
| spellingShingle | Michael DeNiro Falah H Al-Mohanna Osama Alsmadi Futwan A Al-Mohanna The nexus between VEGF and NFκB orchestrates a hypoxia-independent neovasculogenesis. PLoS ONE |
| title | The nexus between VEGF and NFκB orchestrates a hypoxia-independent neovasculogenesis. |
| title_full | The nexus between VEGF and NFκB orchestrates a hypoxia-independent neovasculogenesis. |
| title_fullStr | The nexus between VEGF and NFκB orchestrates a hypoxia-independent neovasculogenesis. |
| title_full_unstemmed | The nexus between VEGF and NFκB orchestrates a hypoxia-independent neovasculogenesis. |
| title_short | The nexus between VEGF and NFκB orchestrates a hypoxia-independent neovasculogenesis. |
| title_sort | nexus between vegf and nfκb orchestrates a hypoxia independent neovasculogenesis |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23533599/pdf/?tool=EBI |
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