Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increased fibronectin, vcam 1 and integrin α4/β1
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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; Montanez, Eloi; Schmid, Bettina.
in: FRONT CELL DEV BIOL, Jahrgang 11, 06.2023, S. 1169962.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increased fibronectin, vcam 1 and integrin α4/β1
AU - Hipke, Katrin
AU - Pitter, Bettina
AU - Hruscha, Alexander
AU - van Bebber, Frauke
AU - Modic, Miha
AU - Bansal, Vikas
AU - Lewandowski, Sebastian A
AU - Orozco, Denise
AU - Edbauer, Dieter
AU - Bonn, Stefan
AU - Haass, Christian
AU - Pohl, Ulrich
AU - Montanez, Eloi
AU - Schmid, Bettina
N1 - Copyright © 2023 Hipke, Pitter, Hruscha, van Bebber, Modic, Bansal, Lewandowski, Orozco, Edbauer, Bonn, Haass, Pohl, Montanez and Schmid.
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
U2 - 10.3389/fcell.2023.1169962
DO - 10.3389/fcell.2023.1169962
M3 - SCORING: Journal article
C2 - 37384248
VL - 11
SP - 1169962
JO - FRONT CELL DEV BIOL
JF - FRONT CELL DEV BIOL
SN - 2296-634X
ER -