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http://hdl.handle.net/2445/200880
Title: | Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increased fibronectin, vcam 1 and integrin α4/β1 |
Author: | Hipke, Katrin Pitter, Bettina Hruscha, Alexander van Bebber, Frauke Modic, Miha Bansal, Vikas Lewandowski, Sebastian A. Orozco, Denise Edbauer, Dieter Bonn, Stefan Haass, Christian Pohl, Ulrich Montañez, Eloi Schmid, Bettina |
Keywords: | Angiogènesi Malalties neurodegeneratives Peix zebra Proteïnes Neovascularization Neurodegenerative Diseases Zebra danio Proteins |
Issue Date: | 13-Jun-2023 |
Publisher: | Frontiers Media |
Abstract: | Aggregation of the Tar DNA-binding protein of 43 kDa (TDP-43) is a pathological hallmark of amyotrophic lateral sclerosis and frontotemporal dementia and likely contributes to disease by loss of nuclear function. Analysis of TDP-43 function in knockout zebrafish identified an endothelial directional migration and hypersprouting phenotype during development prior lethality. In human umbilical vein cells (HUVEC) the loss of TDP-43 leads to hyperbranching. We identified elevated expression of FIBRONECTIN 1 (FN1), the VASCULAR CELL ADHESION MOLECULE 1 (VCAM1), as well as their receptor INTEGRIN α4β1 (ITGA4B1) in HUVEC cells. Importantly, reducing the levels of ITGA4, FN1, and VCAM1 homologues in the TDP-43 loss-of-function zebrafish rescues the angiogenic defects indicating the conservation of human and zebrafish TDP-43 function during angiogenesis. Our study identifies a novel pathway regulated by TDP-43 important for angiogenesis during development. |
Note: | Reproducció del document publicat a: https://doi.org/10.3389/fcell.2023.1169962 |
It is part of: | Frontiers In Cell And Developmental Biology, 2023, vol. 11 |
URI: | http://hdl.handle.net/2445/200880 |
Related resource: | https://doi.org/10.3389/fcell.2023.1169962 |
ISSN: | 2296-634X |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Articles publicats en revistes (Ciències Fisiològiques) |
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