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| Home > Publications Database > Endothelial TDP-43 controls sprouting angiogenesis and vascular barrier integrity, and its deletion triggers neuroinflammation. > print |
| 001 | 268530 | ||
| 005 | 20240808164632.0 | ||
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| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Arribas, Víctor |b 0 |
| 245 | _ | _ | |a Endothelial TDP-43 controls sprouting angiogenesis and vascular barrier integrity, and its deletion triggers neuroinflammation. |
| 260 | _ | _ | |a Ann Arbor, Michigan |c 2024 |b JCI Insight |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 520 | _ | _ | |a 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. |
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| 650 | _ | 7 | |a Angiogenesis |2 Other |
| 650 | _ | 7 | |a Endothelial cells |2 Other |
| 650 | _ | 7 | |a Vascular biology |2 Other |
| 650 | _ | 7 | |a DNA-Binding Proteins |2 NLM Chemicals |
| 650 | _ | 2 | |a Mice |2 MeSH |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a Endothelial Cells: metabolism |2 MeSH |
| 650 | _ | 2 | |a Neuroinflammatory Diseases |2 MeSH |
| 650 | _ | 2 | |a Angiogenesis |2 MeSH |
| 650 | _ | 2 | |a Neovascularization, Physiologic: genetics |2 MeSH |
| 650 | _ | 2 | |a DNA-Binding Proteins: genetics |2 MeSH |
| 650 | _ | 2 | |a DNA-Binding Proteins: metabolism |2 MeSH |
| 700 | 1 | _ | |a Onetti, Yara |b 1 |
| 700 | 1 | _ | |a Ramiro-Pareta, Marina |b 2 |
| 700 | 1 | _ | |a Villacampa, Pilar |b 3 |
| 700 | 1 | _ | |a Beck, Heike |b 4 |
| 700 | 1 | _ | |a Alberola, Mariona |b 5 |
| 700 | 1 | _ | |a Esteve-Codina, Anna |b 6 |
| 700 | 1 | _ | |a Merkel, Angelika |b 7 |
| 700 | 1 | _ | |a Sperandio, Markus |b 8 |
| 700 | 1 | _ | |a Martínez-Estrada, Ofelia M |b 9 |
| 700 | 1 | _ | |a Schmid, Bettina |0 P:(DE-2719)2241638 |b 10 |u dzne |
| 700 | 1 | _ | |a Montanez, Eloi |b 11 |
| 773 | _ | _ | |a 10.1172/jci.insight.177819 |g Vol. 9, no. 5 |0 PERI:(DE-600)2874757-4 |n 5 |p e177819 |t JCI insight |v 9 |y 2024 |x 2379-3708 |
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