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

Autor: Pal S; Department of Immunology, Genetics and Pathology, Beijer and Science for Life Laboratories, Uppsala University, Uppsala, Sweden., Su Y; Department of Immunology, Genetics and Pathology, Beijer and Science for Life Laboratories, Uppsala University, Uppsala, Sweden., Nwadozi E; Department of Immunology, Genetics and Pathology, Beijer and Science for Life Laboratories, Uppsala University, Uppsala, Sweden., Claesson-Welsh L; Department of Immunology, Genetics and Pathology, Beijer and Science for Life Laboratories, Uppsala University, Uppsala, Sweden., Richards M; Department of Immunology, Genetics and Pathology, Beijer and Science for Life Laboratories, Uppsala University, Uppsala, Sweden. mark.richards@igp.uu.se.
Jazyk: angličtina
Zdroj: Angiogenesis [Angiogenesis] 2024 Dec 12; Vol. 28 (1), pp. 7. Date of Electronic Publication: 2024 Dec 12.
DOI: 10.1007/s10456-024-09963-3
Abstrakt: 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.
Competing Interests: Declarations. Conflict of interest: M.R. is now an employee for AstraZeneca (Biopharmaceuticals R&D, Cambridge, UK). All of this work was performed at Dept. of Immunology, Genetics and Pathology, Beijer and Science for Life Laboratories, Uppsala University, Uppsala, Sweden. No funding or support was received from AstraZeneca. Other authors declared no conflict of interest.
(© 2024. The Author(s).)
Databáze: MEDLINE
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