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A deficiency of uPAR alters endothelial angiogenic function and cell morphology
The angiogenic potential of a cell requires dynamic reorganization of the cytoskeletal architecture that involves the interaction of urokinase-type plasminogen activator receptor (uPAR) with the extracellular matrix. This study focuses on the effect of uPAR deficiency (uPAR(-/-)) on angiogenic funct...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105951/ https://www.ncbi.nlm.nih.gov/pubmed/21535874 http://dx.doi.org/10.1186/2045-824X-3-10 |
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author | Balsara, Rashna D Merryman, Reid Virjee, Farhaad Northway, Claire Castellino, Francis J Ploplis, Victoria A |
author_facet | Balsara, Rashna D Merryman, Reid Virjee, Farhaad Northway, Claire Castellino, Francis J Ploplis, Victoria A |
author_sort | Balsara, Rashna D |
collection | PubMed |
description | The angiogenic potential of a cell requires dynamic reorganization of the cytoskeletal architecture that involves the interaction of urokinase-type plasminogen activator receptor (uPAR) with the extracellular matrix. This study focuses on the effect of uPAR deficiency (uPAR(-/-)) on angiogenic function and associated cytoskeletal organization. Utilizing murine endothelial cells, it was observed that adhesion, migration, proliferation, and capillary tube formation were altered in uPAR(-/- )cells compared to wild-type (WT) cells. On a vitronectin (Vn) matrix, uPAR(-/- )cells acquired a "fried egg" morphology characterized by circular actin organization and lack of lamellipodia formation. The up-regulation of β1 integrin, FAK(P-Tyr925), and paxillin (P-Tyr118), and decreased Rac1 activation, suggested increased focal adhesions, but delayed focal adhesion turnover in uPAR(-/- )cells. This accounted for the enhanced adhesion, but attenuated migration, on Vn. VEGF-enriched Matrigel implants from uPAR(-/- )mice demonstrated a lack of mature vessel formation compared to WT mice. Collectively, these results indicate that a uPAR deficiency leads to decreased angiogenic functions of endothelial cells. |
format | Text |
id | pubmed-3105951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-31059512011-06-02 A deficiency of uPAR alters endothelial angiogenic function and cell morphology Balsara, Rashna D Merryman, Reid Virjee, Farhaad Northway, Claire Castellino, Francis J Ploplis, Victoria A Vasc Cell Research The angiogenic potential of a cell requires dynamic reorganization of the cytoskeletal architecture that involves the interaction of urokinase-type plasminogen activator receptor (uPAR) with the extracellular matrix. This study focuses on the effect of uPAR deficiency (uPAR(-/-)) on angiogenic function and associated cytoskeletal organization. Utilizing murine endothelial cells, it was observed that adhesion, migration, proliferation, and capillary tube formation were altered in uPAR(-/- )cells compared to wild-type (WT) cells. On a vitronectin (Vn) matrix, uPAR(-/- )cells acquired a "fried egg" morphology characterized by circular actin organization and lack of lamellipodia formation. The up-regulation of β1 integrin, FAK(P-Tyr925), and paxillin (P-Tyr118), and decreased Rac1 activation, suggested increased focal adhesions, but delayed focal adhesion turnover in uPAR(-/- )cells. This accounted for the enhanced adhesion, but attenuated migration, on Vn. VEGF-enriched Matrigel implants from uPAR(-/- )mice demonstrated a lack of mature vessel formation compared to WT mice. Collectively, these results indicate that a uPAR deficiency leads to decreased angiogenic functions of endothelial cells. BioMed Central 2011-05-02 /pmc/articles/PMC3105951/ /pubmed/21535874 http://dx.doi.org/10.1186/2045-824X-3-10 Text en Copyright ©2011 Balsara et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Balsara, Rashna D Merryman, Reid Virjee, Farhaad Northway, Claire Castellino, Francis J Ploplis, Victoria A A deficiency of uPAR alters endothelial angiogenic function and cell morphology |
title | A deficiency of uPAR alters endothelial angiogenic function and cell morphology |
title_full | A deficiency of uPAR alters endothelial angiogenic function and cell morphology |
title_fullStr | A deficiency of uPAR alters endothelial angiogenic function and cell morphology |
title_full_unstemmed | A deficiency of uPAR alters endothelial angiogenic function and cell morphology |
title_short | A deficiency of uPAR alters endothelial angiogenic function and cell morphology |
title_sort | deficiency of upar alters endothelial angiogenic function and cell morphology |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105951/ https://www.ncbi.nlm.nih.gov/pubmed/21535874 http://dx.doi.org/10.1186/2045-824X-3-10 |
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