2026-06-14T03:35:57Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/124062024-11-29T22:47:44Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Frye, Maike
author
Stritt, Simon
author
Ortsäter, Henrik
author
Hernandez Vasquez, Magda
author
Kaakinen, Mika
author
Vicente, Andres
author
Wiseman, John
author
Eklund, Lauri
author
Vestweber, Dietmar
author
Mäkinen, Taija
author
Martinez Torrecuadrada, Jorge Luis
funder
Swedish Cancer Society (Cancerfonden)
funder
Knut and Alice Wallenberg Foundation
funder
Swedish Research Council
funder
Unión Europea. Comisión Europea. H2020
funder
Deutsche Forschungsgemeinschaft (Alemania)
funder
European Molecular Biology Organization
funder
Comunidad de Madrid (España)
2021-03-23T11:31:52Z
2021-03-23T11:31:52Z
2020-09-08
Elife. 2020 Sep;9:e57732.
10.7554/eLife.57732
2050-084X
eLife
32897857
http://hdl.handle.net/20.500.12105/12406
Endothelial integrity is vital for homeostasis and adjusted to tissue demands. Although fluid uptake by lymphatic capillaries is a critical attribute of the lymphatic vasculature, the barrier function of collecting lymphatic vessels is also important by ensuring efficient fluid drainage as well as lymph node delivery of antigens and immune cells. Here, we identified the transmembrane ligand EphrinB2 and its receptor EphB4 as critical homeostatic regulators of collecting lymphatic vessel integrity. Conditional gene deletion in mice revealed that EphrinB2/EphB4 signalling is dispensable for blood endothelial barrier function, but required for stabilization of lymphatic endothelial cell (LEC) junctions in different organs of juvenile and adult mice. Studies in primary human LECs further showed that basal EphrinB2/EphB4 signalling controls junctional localisation of the tight junction protein CLDN5 and junction stability via Rac1/Rho-mediated regulation of cytoskeletal contractility. EphrinB2/EphB4 signalling therefore provides a potential therapeutic target to selectively modulate lymphatic vessel permeability and function.
eng
EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity.
journal article
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URL
https://repisalud.isciii.es/bitstreams/85a72dfb-8d15-466e-b900-327aeef1e0c9/download
File
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application/pdf
EphrinB2-EphB4signalling_2020.pdf
URL
https://repisalud.isciii.es/bitstreams/d1039d26-f383-4657-8f1c-e82797503ed9/download
File
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text/plain
EphrinB2-EphB4signalling_2020.pdf.txt