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Upregulation of Neogenin-1 by a CREB1-BAF47 Complex in Vascular Endothelial Cells is Implicated in Atherogenesis
Atherosclerosis is generally considered a human pathology of chronic inflammation, to which endothelial dysfunction plays an important role. Here we investigated the role of neogenin 1 (Neo-1) in oxidized low-density lipoprotein (oxLDL) induced endothelial dysfunction focusing on its transcriptional...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851423/ https://www.ncbi.nlm.nih.gov/pubmed/35186922 http://dx.doi.org/10.3389/fcell.2022.803029 |
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author | Li, Nan Liu, Hong Xue, Yujia Chen, Junliang Kong, Xiaocen Zhang, Yuanyuan |
author_facet | Li, Nan Liu, Hong Xue, Yujia Chen, Junliang Kong, Xiaocen Zhang, Yuanyuan |
author_sort | Li, Nan |
collection | PubMed |
description | Atherosclerosis is generally considered a human pathology of chronic inflammation, to which endothelial dysfunction plays an important role. Here we investigated the role of neogenin 1 (Neo-1) in oxidized low-density lipoprotein (oxLDL) induced endothelial dysfunction focusing on its transcriptional regulation. We report that Neo-1 expression was upregulated by oxLDL in both immortalized vascular endothelial cells and primary aortic endothelial cells. Neo-1 knockdown attenuated whereas Neo-1 over-expression enhanced oxLDL-induced leukocyte adhesion to endothelial cells. Neo-1 regulated endothelial-leukocyte interaction by modulating nuclear factor kappa B (NF-κB) activity to alter the expression of adhesion molecules. Neo-1 blockade with a blocking antibody ameliorated atherogenesis in Apoe (−/−) mice fed a Western diet. Ingenuity pathway analysis combined with validation assays confirmed that cAMP response element binding protein 1 (CREB1) and Brg1-associated factor 47 (BAF47) mediated oxLDL induced Neo-1 upregulation. CREB1 interacted with BAF47 and recruited BAF47 to the proximal Neo-1 promoter leading to Neo-1 trans-activation. In conclusion, our data delineate a novel transcriptional mechanism underlying Neo-1 activation in vascular endothelial cells that might contribute to endothelial dysfunction and atherosclerosis. |
format | Online Article Text |
id | pubmed-8851423 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88514232022-02-18 Upregulation of Neogenin-1 by a CREB1-BAF47 Complex in Vascular Endothelial Cells is Implicated in Atherogenesis Li, Nan Liu, Hong Xue, Yujia Chen, Junliang Kong, Xiaocen Zhang, Yuanyuan Front Cell Dev Biol Cell and Developmental Biology Atherosclerosis is generally considered a human pathology of chronic inflammation, to which endothelial dysfunction plays an important role. Here we investigated the role of neogenin 1 (Neo-1) in oxidized low-density lipoprotein (oxLDL) induced endothelial dysfunction focusing on its transcriptional regulation. We report that Neo-1 expression was upregulated by oxLDL in both immortalized vascular endothelial cells and primary aortic endothelial cells. Neo-1 knockdown attenuated whereas Neo-1 over-expression enhanced oxLDL-induced leukocyte adhesion to endothelial cells. Neo-1 regulated endothelial-leukocyte interaction by modulating nuclear factor kappa B (NF-κB) activity to alter the expression of adhesion molecules. Neo-1 blockade with a blocking antibody ameliorated atherogenesis in Apoe (−/−) mice fed a Western diet. Ingenuity pathway analysis combined with validation assays confirmed that cAMP response element binding protein 1 (CREB1) and Brg1-associated factor 47 (BAF47) mediated oxLDL induced Neo-1 upregulation. CREB1 interacted with BAF47 and recruited BAF47 to the proximal Neo-1 promoter leading to Neo-1 trans-activation. In conclusion, our data delineate a novel transcriptional mechanism underlying Neo-1 activation in vascular endothelial cells that might contribute to endothelial dysfunction and atherosclerosis. Frontiers Media S.A. 2022-02-03 /pmc/articles/PMC8851423/ /pubmed/35186922 http://dx.doi.org/10.3389/fcell.2022.803029 Text en Copyright © 2022 Li, Liu, Xue, Chen, Kong and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Li, Nan Liu, Hong Xue, Yujia Chen, Junliang Kong, Xiaocen Zhang, Yuanyuan Upregulation of Neogenin-1 by a CREB1-BAF47 Complex in Vascular Endothelial Cells is Implicated in Atherogenesis |
title | Upregulation of Neogenin-1 by a CREB1-BAF47 Complex in Vascular Endothelial Cells is Implicated in Atherogenesis |
title_full | Upregulation of Neogenin-1 by a CREB1-BAF47 Complex in Vascular Endothelial Cells is Implicated in Atherogenesis |
title_fullStr | Upregulation of Neogenin-1 by a CREB1-BAF47 Complex in Vascular Endothelial Cells is Implicated in Atherogenesis |
title_full_unstemmed | Upregulation of Neogenin-1 by a CREB1-BAF47 Complex in Vascular Endothelial Cells is Implicated in Atherogenesis |
title_short | Upregulation of Neogenin-1 by a CREB1-BAF47 Complex in Vascular Endothelial Cells is Implicated in Atherogenesis |
title_sort | upregulation of neogenin-1 by a creb1-baf47 complex in vascular endothelial cells is implicated in atherogenesis |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851423/ https://www.ncbi.nlm.nih.gov/pubmed/35186922 http://dx.doi.org/10.3389/fcell.2022.803029 |
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