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http://hdl.handle.net/2445/212448
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DC Field | Value | Language |
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dc.contributor.author | Esteve Codina, Anna | - |
dc.contributor.author | Arribas, Víctor | - |
dc.contributor.author | Onetti, Yara | - |
dc.contributor.author | Ramiro Pareta, Marina | - |
dc.contributor.author | Villacampa, Pilar | - |
dc.contributor.author | Beck, Heike | - |
dc.contributor.author | Alberola, Mariona | - |
dc.contributor.author | Merkel, Angelika | - |
dc.contributor.author | Sperandio, Markus | - |
dc.contributor.author | Martínez Estrada, Ofelia María | - |
dc.contributor.author | Schmid, Bettina | - |
dc.contributor.author | Montañez, Eloi | - |
dc.date.accessioned | 2024-06-04T18:07:25Z | - |
dc.date.available | 2024-06-04T18:07:25Z | - |
dc.date.issued | 2024-02-01 | - |
dc.identifier.issn | 2379-3708 | - |
dc.identifier.uri | http://hdl.handle.net/2445/212448 | - |
dc.description.abstract | 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. | - |
dc.format.extent | 19 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | American Society for Clinical Investigation | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1172/jci.insight.177819 | - |
dc.relation.ispartof | JCI Insight, 2024, vol. 9, num.5 | - |
dc.relation.uri | https://doi.org/10.1172/jci.insight.177819 | - |
dc.rights | (c) American Society for Clinical Investigation, 2024 | - |
dc.source | Articles publicats en revistes (Ciències Fisiològiques) | - |
dc.subject.classification | Endoteli | - |
dc.subject.classification | Angiogènesi | - |
dc.subject.classification | Animals | - |
dc.subject.classification | Proteïnes | - |
dc.subject.other | Endothelium | - |
dc.subject.other | Neovascularization | - |
dc.subject.other | Animals | - |
dc.subject.other | Proteins | - |
dc.title | Endothelial TDP-43 controls sprouting angiogenesis and vascular barrier integrity, and its deletion triggers neuroinflammation | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 746290 | - |
dc.date.updated | 2024-06-04T18:07:30Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 38300714 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Articles publicats en revistes (Ciències Fisiològiques) |
Files in This Item:
File | Description | Size | Format | |
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854076.pdf | 32.07 MB | Adobe PDF | View/Open |
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