{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:48:31Z","timestamp":1792000111171,"version":"4.4.0"},"reference-count":53,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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+\/\u2212 mice were used. ECFC silenced for Eng with Eng-siRNA and ctr-siRNA were used to test tubulogenesis and permeability +\/\u2212 TNF\u03b1 and +\/\u2212 LIM kinase inhibitors (LIMKi). In silico modeling of TNF\u03b1\u2013Eng 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\u2013tubulin distribution\/co-localization were evaluated in cells by confocal microscopy. Eng silencing in ECFCs resulted in a decrease of cell sprouting by 50 \u00b1 15% (p &lt; 0.05) and an increase in pseudo-tube width (41 \u00b1 4.5%; p &lt; 0.001) compared to control. Upon TNF\u03b1 stimulation, ECFC Eng\u2013siRNA displayed a significant higher permeability compared to ctr-siRNA (p &lt; 0.01), which is associated to a higher Ca2+ mobilization (p &lt; 0.01). Computational analysis suggested that Eng mitigated TNF\u03b1 activity. F-actin polymerization was significantly increased in ECFC Eng-siRNA, MAEC+\/\u2212, and MLEC+\/\u2212 compared to controls (p &lt; 0.001, p &lt; 0.01, and p &lt; 0.01, respectively) as well as actin\/tubulin distribution (p &lt; 0.01). Furthermore, the inactive form of cofilin (P-cofilin at Ser3) was significantly decreased by 36.7 \u00b1 4.8% in ECFC Eng-siRNA compared to ctr-siRNA (p &lt; 0.001). Interestingly, LIMKi reproduced the absence of Eng on TNF\u03b1-induced ECFC-increased permeability. Our data suggest that Eng plays a critical role in the homeostasis regulation of endothelial cells under inflammatory conditions (TNF\u03b1), and loss of Eng influences ECFC-related permeability through the LIMK\/cofilin\/actin rearrangement-signaling pathway.<\/jats:p>","DOI":"10.3390\/ijms22168837","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T21:27:40Z","timestamp":1629235660000},"page":"8837","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Endoglin Is an Endothelial Housekeeper against Inflammation: Insight in ECFC-Related Permeability through LIMK\/Cofilin Pathway"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0570-6104","authenticated-orcid":false,"given":"Elisa","family":"Rossi","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, University of Paris, F-75006 Paris, France"},{"name":"IThEM, Inserm UMR-S 1140, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4064-8114","authenticated-orcid":false,"given":"Alexandre","family":"Kauskot","sequence":"additional","affiliation":[{"name":"HITh, UMR-S 1176, INSERM\u2014Faculty of Medicine, University Paris-Saclay, F-94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Saller","sequence":"additional","affiliation":[{"name":"HITh, UMR-S 1176, INSERM\u2014Faculty of Medicine, University Paris-Saclay, F-94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0122-7859","authenticated-orcid":false,"given":"Elisa","family":"Frezza","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Paris, F-75006 Paris, France"},{"name":"CiTCoM, CNRS, Universit\u00e9 de Paris, F-75006 Paris, 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6218-0460","authenticated-orcid":false,"given":"Bruno","family":"Saubam\u00e9a","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Paris, F-75006 Paris, France"},{"name":"UMR-S 1144, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9139-2147","authenticated-orcid":false,"given":"Pascale","family":"Gaussem","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Paris, F-75006 Paris, France"},{"name":"IThEM, Inserm UMR-S 1140, F-75006 Paris, France"},{"name":"AP-HP, Hematology Department, H\u00f4pital Europ\u00e9en Georges Pompidou, F-75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0226-482X","authenticated-orcid":false,"given":"Miguel","family":"Pericacho","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Universidad de Salamanca, 37008 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8225-9117","authenticated-orcid":false,"given":"Regis","family":"Bobe","sequence":"additional","affiliation":[{"name":"HITh, UMR-S 1176, INSERM\u2014Faculty of Medicine, University Paris-Saclay, F-94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6264-902X","authenticated-orcid":false,"given":"Christilla","family":"Bachelot-Loza","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Paris, F-75006 Paris, France"},{"name":"IThEM, Inserm UMR-S 1140, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuela","family":"Pasquali","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Paris, F-75006 Paris, France"},{"name":"CiTCoM, CNRS, Universit\u00e9 de Paris, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1563-6162","authenticated-orcid":false,"given":"Carmelo","family":"Bernabeu","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas Margarita Salas, 28040 Madrid, Spain"},{"name":"Consejo Superior de Investigaciones Cient\u00edficas (CSIC) and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7731-9202","authenticated-orcid":false,"given":"David M.","family":"Smadja","sequence":"additional","affiliation":[{"name":"Faculty of 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