Abstract Neuropilin-1 (NRP1) regulates endothelial cell (EC) biology through modulation of vascular endothelial growth factor receptor 2 (VEGFR2) signalling by presenting VEGFA to VEGFR2. How NRP1 impacts VEGFA-mediated vascular hyperpermeability has however remained unresolved, described as exerting either a positive or a passive function. Using EC-specific Nrp1 knock-out mice, we discover that EC-expressed NRP1 exerts an organotypic role. In the ear skin, VEGFA/VEGFR2-mediated vascular leakage was increased following loss of EC NRP1, implicating NRP1 in negative regulation of VEGFR2 signalling. In contrast, in the back skin and trachea, loss of EC NRP1 decreased vascular leakage. In accordance, phosphorylation of vascular endothelial (VE)-cadherin was increased in the ear skin but suppressed in the back skin of Nrp1 iECKO mice. NRP1 expressed on perivascular cells has been shown to impact VEGF-mediated VEGFR2 signalling. Importantly, expression of NRP1 on perivascular cells was more abundant in the ear skin than in the back skin. Global loss of NRP1 resulted in suppressed VEGFA-induced vascular leakage in the ear skin, implicating perivascular NRP1 as a juxtacrine co-receptor of VEGFA in this compartment. Altogether, we demonstrate that perivascular NRP1 is an active participant in EC VEGFA/VEGFR2 signalling and acts as an organotypic modifier of EC biology.

Sagnik Pal

Yangyang Su

Emmanuel Nwadozi

Lena Claesson-Welsh

Mark Richards

Angiogenesis

《血管生成》是一本国际同行评审期刊，致力于发表高质量的原创文章和评论，了解在生理和病理条件下调节血管生成的细胞和分子机制。作为代表全方位血管生成研究的快速交流的中心来源，这本多学科期刊发表使用分子、体外、动物模型系统和血管生成疾病临床研究的创新实验研究。血管生成还报道了促进或抑制血管生成的新治疗方法以及疾病诊断和预后的新标志物和技术。

Angiogenesis is an international peer-reviewed journal dedicated to publishing high-quality original research and reviews that explore the cellular and molecular mechanisms regulating angiogenesis under physiological and pathological conditions. As a central source for rapid communication in the field of angiogenesis research, this multidisciplinary journal publishes innovative experimental studies utilizing molecular, in vitro, animal model systems, and clinical research on angiogenesis-related diseases. Angiogenesis also reports on new therapeutic approaches that promote or inhibit angiogenesis, as well as novel biomarkers and techniques for disease diagnosis and prognosis.

《Angiogenesis》是一本国际同行评审期刊，专注于发表高质量的原创研究和评论，探讨在生理和病理条件下调节血管生成的细胞和分子机制。作为血管生成研究的快速交流中心，这本多学科期刊发表基于分子、体外实验、动物模型和临床研究的创新实验成果。《Angiogenesis》还报道了促进或抑制血管生成的新治疗方法，以及疾病诊断和预后的新标志物和技术。

Category	Quartile
医学	1
医学, 外周血管病	2

Neuropilin-1 controls vascular permeability through juxtacrine regulation of endothelial adherens junctions

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Journal Info

Category	Quartile
PERIPHERAL VASCULAR DISEASE	1