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Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increased fibronectin, vcam 1 and integrin α4/β1 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 Angiogènesi Malalties neurodegeneratives Peix zebra Proteïnes Neovascularization Neurodegenerative Diseases Zebra danio Proteins 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. 2023-07-19T08:52:06Z 2023-07-19T08:52:06Z 2023-06-13 2023-07-19T08:52:06Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 2296-634X https://hdl.handle.net/2445/200880 737844 37384248 eng Reproducció del document publicat a: https://doi.org/10.3389/fcell.2023.1169962 Frontiers In Cell And Developmental Biology, 2023, vol. 11 https://doi.org/10.3389/fcell.2023.1169962 cc-by (c) Hipke, Katrin et al., 2023 https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess 15 p. application/pdf Frontiers Media Articles publicats en revistes (Ciències Fisiològiques)