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Netrin-4 promotes mural cell adhesion and recruitment to endothelial cells
Netrins are secreted molecules involved in axon guidance and angiogenesis. We previously showed that Netrin-4 acts as an anti-angiogenic factor by inhibiting endothelial cell (EC) functions. In this study, we investigated the effects of Netrin-4 on vascular smooth muscle cell (VSMC) activity in vitr...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909532/ https://www.ncbi.nlm.nih.gov/pubmed/24472220 http://dx.doi.org/10.1186/2045-824X-6-1 |
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author | Lejmi, Esma Bouras, Ilyes Camelo, Serge Roumieux, Marie Minet, Norbert Leré-Déan, Carole Merkulova-Rainon, Tatyana Autret, Gwennhael Vayssettes, Catherine Clement, Olivier Plouët, Jean Leconte, Laurence |
author_facet | Lejmi, Esma Bouras, Ilyes Camelo, Serge Roumieux, Marie Minet, Norbert Leré-Déan, Carole Merkulova-Rainon, Tatyana Autret, Gwennhael Vayssettes, Catherine Clement, Olivier Plouët, Jean Leconte, Laurence |
author_sort | Lejmi, Esma |
collection | PubMed |
description | Netrins are secreted molecules involved in axon guidance and angiogenesis. We previously showed that Netrin-4 acts as an anti-angiogenic factor by inhibiting endothelial cell (EC) functions. In this study, we investigated the effects of Netrin-4 on vascular smooth muscle cell (VSMC) activity in vitro and in vivo. We show that exogenous Netrin-4 stimulated VSMC adhesion and migration, and increased their coverage on EC tubes (grown on a Matrigel substrate). siRNA knock-down of endogenous Netrin-4 expression in VSMC decreased their recruitment to EC tubes. VSMC expressed Netrin-4 and three of the six Netrin-1 cognate receptors: DCC, Neogenin, and Unc5B. Silencing of these receptors reduced Netrin-4 adhesion to VSMC, strongly suggesting that these receptors were involved in the recruitment process. We previously showed that Netrin-4 overexpression in PC3 cancer cells delayed tumor growth in a model of subcutaneous xenograft by reducing tumor vessel density. Here, we show that Netrin-4 overexpression improved tumor blood vessel structure and increased VSMC coverage. Thus, Netrin-4 induced mural cell recruitment may play a role in the inhibition of tumor growth. Our data suggest that Netrin-4 is important for blood vessel normalization through the regulation of both endothelial and perivascular cells. |
format | Online Article Text |
id | pubmed-3909532 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-39095322014-02-02 Netrin-4 promotes mural cell adhesion and recruitment to endothelial cells Lejmi, Esma Bouras, Ilyes Camelo, Serge Roumieux, Marie Minet, Norbert Leré-Déan, Carole Merkulova-Rainon, Tatyana Autret, Gwennhael Vayssettes, Catherine Clement, Olivier Plouët, Jean Leconte, Laurence Vasc Cell Research Netrins are secreted molecules involved in axon guidance and angiogenesis. We previously showed that Netrin-4 acts as an anti-angiogenic factor by inhibiting endothelial cell (EC) functions. In this study, we investigated the effects of Netrin-4 on vascular smooth muscle cell (VSMC) activity in vitro and in vivo. We show that exogenous Netrin-4 stimulated VSMC adhesion and migration, and increased their coverage on EC tubes (grown on a Matrigel substrate). siRNA knock-down of endogenous Netrin-4 expression in VSMC decreased their recruitment to EC tubes. VSMC expressed Netrin-4 and three of the six Netrin-1 cognate receptors: DCC, Neogenin, and Unc5B. Silencing of these receptors reduced Netrin-4 adhesion to VSMC, strongly suggesting that these receptors were involved in the recruitment process. We previously showed that Netrin-4 overexpression in PC3 cancer cells delayed tumor growth in a model of subcutaneous xenograft by reducing tumor vessel density. Here, we show that Netrin-4 overexpression improved tumor blood vessel structure and increased VSMC coverage. Thus, Netrin-4 induced mural cell recruitment may play a role in the inhibition of tumor growth. Our data suggest that Netrin-4 is important for blood vessel normalization through the regulation of both endothelial and perivascular cells. BioMed Central 2014-01-28 /pmc/articles/PMC3909532/ /pubmed/24472220 http://dx.doi.org/10.1186/2045-824X-6-1 Text en Copyright © 2014 Lejmi 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 Lejmi, Esma Bouras, Ilyes Camelo, Serge Roumieux, Marie Minet, Norbert Leré-Déan, Carole Merkulova-Rainon, Tatyana Autret, Gwennhael Vayssettes, Catherine Clement, Olivier Plouët, Jean Leconte, Laurence Netrin-4 promotes mural cell adhesion and recruitment to endothelial cells |
title | Netrin-4 promotes mural cell adhesion and recruitment to endothelial cells |
title_full | Netrin-4 promotes mural cell adhesion and recruitment to endothelial cells |
title_fullStr | Netrin-4 promotes mural cell adhesion and recruitment to endothelial cells |
title_full_unstemmed | Netrin-4 promotes mural cell adhesion and recruitment to endothelial cells |
title_short | Netrin-4 promotes mural cell adhesion and recruitment to endothelial cells |
title_sort | netrin-4 promotes mural cell adhesion and recruitment to endothelial cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909532/ https://www.ncbi.nlm.nih.gov/pubmed/24472220 http://dx.doi.org/10.1186/2045-824X-6-1 |
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