Esteve Codina, AnnaArribas, VíctorOnetti, YaraRamiro Pareta, MarinaVillacampa, PilarBeck, HeikeAlberola, MarionaMerkel, AngelikaSperandio, MarkusMartínez Estrada, Ofelia MaríaSchmid, BettinaMontañez, Eloi2024-06-042024-06-042024-02-012379-3708https://hdl.handle.net/2445/212448TAR 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.19 p.application/pdfeng(c) American Society for Clinical Investigation, 2024EndoteliAngiogènesiAnimalsProteïnesEndotheliumNeovascularizationAnimalsProteinsinfo:eu-repo/semantics/article7462902024-06-04info:eu-repo/semantics/openAccess38300714