%0 Journal Article
%A Arribas, Víctor
%A Onetti, Yara
%A Ramiro-Pareta, Marina
%A Villacampa, Pilar
%A Beck, Heike
%A Alberola, Mariona
%A Esteve-Codina, Anna
%A Merkel, Angelika
%A Sperandio, Markus
%A Martínez-Estrada, Ofelia M
%A Schmid, Bettina
%A Montanez, Eloi
%T Endothelial TDP-43 controls sprouting angiogenesis and vascular barrier integrity, and its deletion triggers neuroinflammation.
%J JCI insight
%V 9
%N 5
%@ 2379-3708
%C Ann Arbor, Michigan
%I JCI Insight
%M DZNE-2024-00271
%P e177819
%D 2024
%X TAR DNA-binding protein 43 (TDP-43) is a DNA/RNA-binding protein that regulates gene expression, and its malfunction in neurons has been causally associated with multiple neurodegenerative disorders. Although progress has been made in understanding the functions of TDP-43 in neurons, little is known about its roles in endothelial cells (ECs), angiogenesis, and vascular function. Using inducible EC-specific TDP-43-KO mice, we showed that TDP-43 is required for sprouting angiogenesis, vascular barrier integrity, and blood vessel stability. Postnatal EC-specific deletion of TDP-43 led to retinal hypovascularization due to defects in vessel sprouting associated with reduced EC proliferation and migration. In mature blood vessels, loss of TDP-43 disrupted the blood-brain barrier and triggered vascular degeneration. These vascular defects were associated with an inflammatory response in the CNS with activation of microglia and astrocytes. Mechanistically, deletion of TDP-43 disrupted the fibronectin matrix around sprouting vessels and reduced β-catenin signaling in ECs. Together, our results indicate that TDP-43 is essential for the formation of a stable and mature vasculature.
%K Mice
%K Animals
%K Endothelial Cells: metabolism
%K Neuroinflammatory Diseases
%K Angiogenesis
%K Neovascularization, Physiologic: genetics
%K DNA-Binding Proteins: genetics
%K DNA-Binding Proteins: metabolism
%K Angiogenesis (Other)
%K Endothelial cells (Other)
%K Vascular biology (Other)
%K DNA-Binding Proteins (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%2 pmc:PMC11143933
%$ pmid:38300714
%R 10.1172/jci.insight.177819
%U https://pub.dzne.de/record/268530