VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis
During angiogenic sprouting, endothelial tip cells emerge from existing vessels in a process that requires vascular basement membrane degradation. Here, we show that F-actin/cortactin/P-Src-based matrix-degrading microdomains called podosomes contribute to this step. In vitro, VEGF-A/Notch signaling...
| Authors: | ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2016 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/155801 |
| Online Access: | https://hdl.handle.net/2445/155801 |
| Access Level: | Open access |
| Keyword: | Col·lagen Genètica Metabolisme Factor de creixement de l'endoteli vascular Collagen Genetics Metabolism Vascular endothelial growth factors |
| _version_ | 1878741006391705600 |
|---|---|
| author | Spuul, Pirjo |
| author2 | Daubon, Thomas Pitter, Bettina Alonso, Florian Fremaux, Isabelle Kramer, Ijsbrand Montañez, Eloi Génot, Elisabeth |
| author2_role | author author author author author author author |
| author_browse | Alonso, Florian Daubon, Thomas Fremaux, Isabelle Génot, Elisabeth Kramer, Ijsbrand Montañez, Eloi Pitter, Bettina Spuul, Pirjo |
| author_facet | Spuul, Pirjo Daubon, Thomas Pitter, Bettina Alonso, Florian Fremaux, Isabelle Kramer, Ijsbrand Montañez, Eloi Génot, Elisabeth |
| author_role | author |
| collection | Dipòsit Digital de la UB |
| description | During angiogenic sprouting, endothelial tip cells emerge from existing vessels in a process that requires vascular basement membrane degradation. Here, we show that F-actin/cortactin/P-Src-based matrix-degrading microdomains called podosomes contribute to this step. In vitro, VEGF-A/Notch signaling regulates the formation of functional podosomes in endothelial cells. Using a retinal neovascularization model, we demonstrate that tip cells assemble podosomes during physiological angiogenesis in vivo. In the retina, podosomes are also part of an interconnected network that surrounds large microvessels and impinges on the underlying basement membrane. Consistently, collagen-IV is scarce in podosome areas. Moreover, Notch inhibition exacerbates podosome formation and collagen-IV loss. We propose that the localized proteolytic action of podosomes on basement membrane collagen-IV facilitates endothelial cell sprouting and anastomosis within the developing vasculature. The identification of podosomes as key components of the sprouting machinery provides another opportunity to target angiogenesis therapeutically. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_dd6333c7d01f7e3d441ebbef9f94ab20 |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/155801 |
| publishDate | 2016 |
| publishDateSort | 2016 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| reponame_str | Dipòsit Digital de la UB |
| spelling | VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis Spuul, Pirjo Daubon, Thomas Pitter, Bettina Alonso, Florian Fremaux, Isabelle Kramer, Ijsbrand Montañez, Eloi Génot, Elisabeth Col·lagen Genètica Metabolisme Factor de creixement de l'endoteli vascular Collagen Genetics Metabolism Vascular endothelial growth factors During angiogenic sprouting, endothelial tip cells emerge from existing vessels in a process that requires vascular basement membrane degradation. Here, we show that F-actin/cortactin/P-Src-based matrix-degrading microdomains called podosomes contribute to this step. In vitro, VEGF-A/Notch signaling regulates the formation of functional podosomes in endothelial cells. Using a retinal neovascularization model, we demonstrate that tip cells assemble podosomes during physiological angiogenesis in vivo. In the retina, podosomes are also part of an interconnected network that surrounds large microvessels and impinges on the underlying basement membrane. Consistently, collagen-IV is scarce in podosome areas. Moreover, Notch inhibition exacerbates podosome formation and collagen-IV loss. We propose that the localized proteolytic action of podosomes on basement membrane collagen-IV facilitates endothelial cell sprouting and anastomosis within the developing vasculature. The identification of podosomes as key components of the sprouting machinery provides another opportunity to target angiogenesis therapeutically. Elsevier https://hdl.handle.net/2445/155801 |
| spellingShingle | VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis Spuul, Pirjo Col·lagen Genètica Metabolisme Factor de creixement de l'endoteli vascular Collagen Genetics Metabolism Vascular endothelial growth factors |
| status_str | publishedVersion |
| title | VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis |
| title_full | VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis |
| title_fullStr | VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis |
| title_full_unstemmed | VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis |
| title_short | VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis |
| title_sort | VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis |
| topic | Col·lagen Genètica Metabolisme Factor de creixement de l'endoteli vascular Collagen Genetics Metabolism Vascular endothelial growth factors |
| topic_facet | Col·lagen Genètica Metabolisme Factor de creixement de l'endoteli vascular Collagen Genetics Metabolism Vascular endothelial growth factors |
| url | https://hdl.handle.net/2445/155801 |