Endoglin Is an endothelial housekeeper against inflammation: insight in ECFC-related permeability through LIMK/cofilin pathway
16 p.-5 fig.
| Autores: | , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/260324 |
| Acceso en línea: | http://hdl.handle.net/10261/260324 |
| Access Level: | acceso abierto |
| Palabra clave: | Endoglin ECFC Cofilin HHT1 TNFα |
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Endoglin Is an endothelial housekeeper against inflammation: insight in ECFC-related permeability through LIMK/cofilin pathwayRossi, ElisaKauskot, AlexandreSaller, FrançoisFrezza, ElisaPoirault-Chassac, SoniaLokajczyk, AnnaBourdoncle, PierreSaubaméa, BrunoGaussem, PascalePericacho, MiguelBobe, RegisBachelot-Loza, ChristillaPasquali, SamuelaBernabéu, CarmeloSmadja, David M.EndoglinECFCCofilinHHT1TNFα16 p.-5 fig.Endoglin (Eng) is an endothelial cell (EC) transmembrane glycoprotein involved in adhesion and angiogenesis. Eng mutations result in vessel abnormalities as observed in hereditary hemorrhagic telangiectasia of type 1. The role of Eng was investigated in endothelial functions and permeability under inflammatory conditions, focusing on the actin dynamic signaling pathway. Endothelial Colony-Forming Cells (ECFC) from human cord blood and mouse lung/aortic EC (MLEC, MAEC) from Eng+/+ and Eng+/− mice were used. ECFC silenced for Eng with Eng-siRNA and ctr-siRNA were used to test tubulogenesis and permeability +/− TNFα and +/− LIM kinase inhibitors (LIMKi). In silico modeling of TNFα–Eng interactions was carried out from PDB IDs 5HZW and 5HZV. Calcium ions (Ca2+) flux was studied by Oregon Green 488 in epifluorescence microscopy. Levels of cofilin phosphorylation and tubulin post-translational modifications were evaluated by Western blot. F-actin and actin–tubulin distribution/co-localization were evaluated in cells by confocal microscopy. Eng silencing in ECFCs resulted in a decrease of cell sprouting by 50 ± 15% (p < 0.05) and an increase in pseudo-tube width (41 ± 4.5%; p < 0.001) compared to control. Upon TNFα stimulation, ECFC Eng–siRNA displayed a significant higher permeability compared to ctr-siRNA (p < 0.01), which is associated to a higher Ca2+ mobilization (p < 0.01). Computational analysis suggested that Eng mitigated TNFα activity. F-actin polymerization was significantly increased in ECFC Eng-siRNA, MAEC+/−, and MLEC+/− compared to controls (p < 0.001, p < 0.01, and p < 0.01, respectively) as well as actin/tubulin distribution (p < 0.01). Furthermore, the inactive form of cofilin (P-cofilin at Ser3) was significantly decreased by 36.7 ± 4.8% in ECFC Eng-siRNA compared to ctr-siRNA (p < 0.001). Interestingly, LIMKi reproduced the absence of Eng on TNFα-induced ECFC-increased permeability. Our data suggest that Eng plays a critical role in the homeostasis regulation of endothelial cells under inflammatory conditions (TNFα), and loss of Eng influences ECFC-related permeability through the LIMK/cofilin/actin rearrangement-signaling pathway.This research was funded by Promex Stiftung für die Forschung Foundation, University of Paris and Institut National de la Santé et de la Recherche Médicale (INSERM).Peer reviewedMultidisciplinary Digital Publishing InstitutePromex Stiftung Fur Die ForschungUniversité de ParisInstitut National de la Santé et de la Recherche Médicale (France)Rossi, Elisa [0000-0002-0570-6104]Kauskot, Alexandre [0000-0002-4064-8114]Saller, François [0000-0001-5255-2630]Frezza, Elisa [0000-0003-0122-7859]Saubaméa, Bruno [0000-0002-6218-0460]Gaussem, Pascale [0000-0002-9139-2147]Pericacho, Miguel [0000-0003-0226-482X]Bobe, Regis [0000-0002-8225-9117]Bachelot-Loza, Christilla [0000-0002-6264-902X ]Pasquali, Samuela [0000-0003-1487-0894]Bernabéu, Carmelo [0000-0002-1563-6162]Smadja, David M. [0000-0001-7731-9202]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202220222021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/260324reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.3390/ijms22168837Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2603242026-05-22T06:33:51Z |
| dc.title.none.fl_str_mv |
Endoglin Is an endothelial housekeeper against inflammation: insight in ECFC-related permeability through LIMK/cofilin pathway |
| title |
Endoglin Is an endothelial housekeeper against inflammation: insight in ECFC-related permeability through LIMK/cofilin pathway |
| spellingShingle |
Endoglin Is an endothelial housekeeper against inflammation: insight in ECFC-related permeability through LIMK/cofilin pathway Rossi, Elisa Endoglin ECFC Cofilin HHT1 TNFα |
| title_short |
Endoglin Is an endothelial housekeeper against inflammation: insight in ECFC-related permeability through LIMK/cofilin pathway |
| title_full |
Endoglin Is an endothelial housekeeper against inflammation: insight in ECFC-related permeability through LIMK/cofilin pathway |
| title_fullStr |
Endoglin Is an endothelial housekeeper against inflammation: insight in ECFC-related permeability through LIMK/cofilin pathway |
| title_full_unstemmed |
Endoglin Is an endothelial housekeeper against inflammation: insight in ECFC-related permeability through LIMK/cofilin pathway |
| title_sort |
Endoglin Is an endothelial housekeeper against inflammation: insight in ECFC-related permeability through LIMK/cofilin pathway |
| dc.creator.none.fl_str_mv |
Rossi, Elisa Kauskot, Alexandre Saller, François Frezza, Elisa Poirault-Chassac, Sonia Lokajczyk, Anna Bourdoncle, Pierre Saubaméa, Bruno Gaussem, Pascale Pericacho, Miguel Bobe, Regis Bachelot-Loza, Christilla Pasquali, Samuela Bernabéu, Carmelo Smadja, David M. |
| author |
Rossi, Elisa |
| author_facet |
Rossi, Elisa Kauskot, Alexandre Saller, François Frezza, Elisa Poirault-Chassac, Sonia Lokajczyk, Anna Bourdoncle, Pierre Saubaméa, Bruno Gaussem, Pascale Pericacho, Miguel Bobe, Regis Bachelot-Loza, Christilla Pasquali, Samuela Bernabéu, Carmelo Smadja, David M. |
| author_role |
author |
| author2 |
Kauskot, Alexandre Saller, François Frezza, Elisa Poirault-Chassac, Sonia Lokajczyk, Anna Bourdoncle, Pierre Saubaméa, Bruno Gaussem, Pascale Pericacho, Miguel Bobe, Regis Bachelot-Loza, Christilla Pasquali, Samuela Bernabéu, Carmelo Smadja, David M. |
| author2_role |
author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Promex Stiftung Fur Die Forschung Université de Paris Institut National de la Santé et de la Recherche Médicale (France) Rossi, Elisa [0000-0002-0570-6104] Kauskot, Alexandre [0000-0002-4064-8114] Saller, François [0000-0001-5255-2630] Frezza, Elisa [0000-0003-0122-7859] Saubaméa, Bruno [0000-0002-6218-0460] Gaussem, Pascale [0000-0002-9139-2147] Pericacho, Miguel [0000-0003-0226-482X] Bobe, Regis [0000-0002-8225-9117] Bachelot-Loza, Christilla [0000-0002-6264-902X ] Pasquali, Samuela [0000-0003-1487-0894] Bernabéu, Carmelo [0000-0002-1563-6162] Smadja, David M. [0000-0001-7731-9202] Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
Endoglin ECFC Cofilin HHT1 TNFα |
| topic |
Endoglin ECFC Cofilin HHT1 TNFα |
| description |
16 p.-5 fig. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021 2022 2022 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10261/260324 |
| url |
http://hdl.handle.net/10261/260324 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
https://doi.org/10.3390/ijms22168837 Sí |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute |
| publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute |
| dc.source.none.fl_str_mv |
reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
| reponame_str |
DIGITAL.CSIC. Repositorio Institucional del CSIC |
| collection |
DIGITAL.CSIC. Repositorio Institucional del CSIC |
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1869413731541188608 |
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15,812429 |