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DataSheet1_Upregulation of Neogenin-1 by a CREB1-BAF47 Complex in Vascular Endothelial Cells is Implicated in Atherogenesis.docx
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.
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References
- https://doi.org//10.1016/s0021-9150%2803%2900097-2
- https://doi.org//10.1016/j.jvssci.2021.04.001
- https://doi.org//10.1182/blood-2011-02-339473
- https://doi.org//10.3389/fcell.2020.00774
- https://doi.org//10.1016/j.redox.2020.101718
- https://doi.org//10.1096/fasebj.9.10.7542214
- https://doi.org//10.1016/s0891-5849%2896%2900271-7
- https://doi.org//10.1161/atvbaha.107.149179
- https://doi.org//10.1016/j.cmet.2008.08.016
- https://doi.org//10.1161/circresaha.115.306301
- https://doi.org//10.1007/s00395-009-0036-0
- https://doi.org//10.1073/pnas.1911024116
- https://doi.org//10.4049/jimmunol.1000193
- https://doi.org//10.1038/s41467-018-07495-1
- https://doi.org//10.3389/fcell.2020.587502
- https://doi.org//10.3389/fcell.2021.687169
- https://doi.org//10.1016/j.cellsig.2004.05.001
- https://doi.org//10.1016/j.cell.2013.02.036
- https://doi.org//10.1172/jci117776
- https://doi.org//10.1371/journal.pone.0032145
- https://doi.org//10.1126/scisignal.2004214
- https://doi.org//10.1172/jci1568
- https://doi.org//10.3389/fcell.2020.00794
- https://doi.org//10.3389/fcell.2020.592048
- https://doi.org//10.1161/circresaha.116.301313
- https://doi.org//10.1016/j.immuni.2013.06.009
- https://doi.org//10.1038/s41569-021-00609-1
- https://doi.org//10.1038/s41586-021-03392-8
- https://doi.org//10.1093/cvr/cvab110
- https://doi.org//10.1007/s000180050006
- https://doi.org//10.3389/fcell.2021.745985
- https://doi.org//10.1016/j.redox.2020.101622
- https://doi.org//10.1016/j.redox.2021.101885
- https://doi.org//10.1074/jbc.m414144200
- https://doi.org//10.1096/fj.11-200063
- https://doi.org//10.1161/circulationaha.105.578955
- https://doi.org//10.1161/01.cir.99.13.1726
- https://doi.org//10.1073/pnas.0405984101
- https://doi.org//10.1186/s13287-017-0494-5
- https://doi.org//10.1056/nejmoa1707914
- https://doi.org//10.15420/cfr.2016%3A25%3A2
- https://doi.org//10.1161/atvbaha.109.199133
- https://doi.org//10.1097/ccm.0000000000000485
- https://doi.org//10.1172/jci128681
- https://doi.org//10.1161/atvbaha.108.179697
- https://doi.org//10.1172/jci11830
- https://doi.org//10.1016/s0021-9150%2800%2900465-2
- https://doi.org//10.1038/ni.2205
- https://doi.org//10.1016/j.redox.2020.101479
- https://doi.org//10.1016/j.redox.2019.101319
- https://doi.org//10.1016/j.biocel.2006.10.023
- https://doi.org//10.1172/jci136908
- https://doi.org//10.3389/fcell.2021.698254
- https://doi.org//10.1172/jci132372
- https://doi.org//10.3389/fcell.2020.578790