粘合连接
神经肽1
细胞生物学
促炎细胞因子
钙粘蛋白
内皮
罗亚
信号转导
炎症
化学
生物
免疫学
癌症研究
细胞
血管内皮生长因子
内分泌学
生物化学
血管内皮生长因子受体
作者
Emy Bosseboeuf,Anissa Chikh,Ahmed Bey Chaker,Tom P Mitchell,Dhilakshani Vignaraja,Ridhi Rajendrakumar,Rayomand S Khambata,Thomas D. Nightingale,Justin C. Mason,Anna M. Randi,Amrita Ahluwalia,Claudio Raimondi
出处
期刊:Science Signaling
[American Association for the Advancement of Science (AAAS)]
日期:2023-05-23
卷期号:16 (786)
被引量:6
标识
DOI:10.1126/scisignal.abo4863
摘要
Linear and disturbed flow differentially regulate gene expression, with disturbed flow priming endothelial cells (ECs) for a proinflammatory, atheroprone expression profile and phenotype. Here, we investigated the role of the transmembrane protein neuropilin-1 (NRP1) in ECs exposed to flow using cultured ECs, mice with an endothelium-specific knockout of NRP1, and a mouse model of atherosclerosis. We demonstrated that NRP1 was a constituent of adherens junctions that interacted with VE-cadherin and promoted its association with p120 catenin, stabilizing adherens junctions and inducing cytoskeletal remodeling in alignment with the direction of flow. We also showed that NRP1 interacted with transforming growth factor-β (TGF-β) receptor II (TGFBR2) and reduced the plasma membrane localization of TGFBR2 and TGF-β signaling. NRP1 knockdown increased the abundance of proinflammatory cytokines and adhesion molecules, resulting in increased leukocyte rolling and atherosclerotic plaque size. These findings describe a role for NRP1 in promoting endothelial function and reveal a mechanism by which NRP1 reduction in ECs may contribute to vascular disease by modulating adherens junction signaling and promoting TGF-β signaling and inflammation.
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