biostudies-literatureArribas VGerman Research Foundationpanish Ministry of Science, Innovation and UniversitiesFundació la Marato TV3Spanish Ministry of Science, Innovation and Universitiese177819https://www.ebi.ac.uk/biostudies/studies/S-EPMC11143933biostudies-literatureUnknown9(5)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 vJCI insightEndothelial TDP-43 controls sprouting angiogenesis and vascular barrier integrity, and its deletion triggers neuroinflammation.PMC11143933TRR359PID2020-119315GB-I00202327 10PID2022-141840OB-I00PID2021-124400OA-I00PID2019-108902GB-I00TRR332Onetti YSperandio MMartinez-Estrada OMSchmid BMerkel ARamiro-Pareta MMontanez EVillacampa PAlberola MEsteve-Codina AArribas VBeck HfalseEndothelial TDP-43 controls sprouting angiogenesis and vascular barrier integrity, and its deletion triggers neuroinflammation.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 v2024-01-01T00:00:00Z2024 Feb2026-06-02T08:32:45.078Z2026-04-16T03:11:31.76ZS-EPMC111439333830071410.1172/jci.insight.177819