Angiopoietin-like 4-Induced 3D Capillary Morphogenesis Correlates to Stabilization of Endothelial Adherens Junctions and Restriction of VEGF-Induced Sprouting
Angiopoietin-like 4 (ANGPTL4) is a target of hypoxia that accumulates in the endothelial extracellular matrix. While ANGPTL4 is known to regulate angiogenesis and vascular permeability, its context-dependent role related to vascular endothelial growth factor (VEGF) has been suggested in capillary mo...
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MDPI AG
2022-01-01
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| Online Access: | https://www.mdpi.com/2227-9059/10/2/206 |
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| author | Athanasia Liabotis Corinne Ardidie-Robouant Philippe Mailly Samaher Besbes Charly Gutierrez Yoann Atlas Laurent Muller Stéphane Germain Catherine Monnot |
| author_facet | Athanasia Liabotis Corinne Ardidie-Robouant Philippe Mailly Samaher Besbes Charly Gutierrez Yoann Atlas Laurent Muller Stéphane Germain Catherine Monnot |
| author_sort | Athanasia Liabotis |
| collection | DOAJ |
| description | Angiopoietin-like 4 (ANGPTL4) is a target of hypoxia that accumulates in the endothelial extracellular matrix. While ANGPTL4 is known to regulate angiogenesis and vascular permeability, its context-dependent role related to vascular endothelial growth factor (VEGF) has been suggested in capillary morphogenesis. We here thus develop in vitro 3D models coupled to imaging and morphometric analysis of capillaries to decipher ANGPTL4 functions either alone or in the presence of VEGF. ANGPTL4 induces the formation of barely branched and thin endothelial capillaries that display linear adherens junctions. However, ANGPTL4 counteracts VEGF-induced formation of abundant ramified capillaries presenting cell–cell junctions characterized by VE-cadherin containing reticular plaques and serrated structures. We further deciphered the early angiogenesis steps regulated by ANGPTL4. During the initial activation of endothelial cells, ANGPTL4 alone induces cell shape changes but limits the VEGF-induced cell elongation and unjamming. In the growing sprout, ANGPTL4 maintains cohesive VE-cadherin pattern and sustains moderate 3D cell migration but restricts VEGF-induced endothelium remodeling and cell migration. This effect is mediated by differential short- and long-term regulation of P-Y1175-VEGFR2 and ERK1-2 signaling by ANGPTL4. Our in vitro 3D models thus provide the first evidence that ANGPTL4 induces a specific capillary morphogenesis but also overcomes VEGF effect. |
| first_indexed | 2024-03-09T22:33:31Z |
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| institution | Directory Open Access Journal |
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| last_indexed | 2024-03-09T22:33:31Z |
| publishDate | 2022-01-01 |
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| series | Biomedicines |
| spelling | doaj.art-159152695c0644e49df0f40fdb61c5072023-11-23T18:51:57ZengMDPI AGBiomedicines2227-90592022-01-0110220610.3390/biomedicines10020206Angiopoietin-like 4-Induced 3D Capillary Morphogenesis Correlates to Stabilization of Endothelial Adherens Junctions and Restriction of VEGF-Induced SproutingAthanasia Liabotis0Corinne Ardidie-Robouant1Philippe Mailly2Samaher Besbes3Charly Gutierrez4Yoann Atlas5Laurent Muller6Stéphane Germain7Catherine Monnot8Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, F-75005 Paris, FranceCenter for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, F-75005 Paris, FranceCenter for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, F-75005 Paris, FranceCenter for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, F-75005 Paris, FranceCenter for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, F-75005 Paris, FranceCenter for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, F-75005 Paris, FranceCenter for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, F-75005 Paris, FranceCenter for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, F-75005 Paris, FranceCenter for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, F-75005 Paris, FranceAngiopoietin-like 4 (ANGPTL4) is a target of hypoxia that accumulates in the endothelial extracellular matrix. While ANGPTL4 is known to regulate angiogenesis and vascular permeability, its context-dependent role related to vascular endothelial growth factor (VEGF) has been suggested in capillary morphogenesis. We here thus develop in vitro 3D models coupled to imaging and morphometric analysis of capillaries to decipher ANGPTL4 functions either alone or in the presence of VEGF. ANGPTL4 induces the formation of barely branched and thin endothelial capillaries that display linear adherens junctions. However, ANGPTL4 counteracts VEGF-induced formation of abundant ramified capillaries presenting cell–cell junctions characterized by VE-cadherin containing reticular plaques and serrated structures. We further deciphered the early angiogenesis steps regulated by ANGPTL4. During the initial activation of endothelial cells, ANGPTL4 alone induces cell shape changes but limits the VEGF-induced cell elongation and unjamming. In the growing sprout, ANGPTL4 maintains cohesive VE-cadherin pattern and sustains moderate 3D cell migration but restricts VEGF-induced endothelium remodeling and cell migration. This effect is mediated by differential short- and long-term regulation of P-Y1175-VEGFR2 and ERK1-2 signaling by ANGPTL4. Our in vitro 3D models thus provide the first evidence that ANGPTL4 induces a specific capillary morphogenesis but also overcomes VEGF effect.https://www.mdpi.com/2227-9059/10/2/206angiopoietin-like 4vascular endothelial growth factorangiogenesisadherens junctionin vitro 3D modelvascularization |
| spellingShingle | Athanasia Liabotis Corinne Ardidie-Robouant Philippe Mailly Samaher Besbes Charly Gutierrez Yoann Atlas Laurent Muller Stéphane Germain Catherine Monnot Angiopoietin-like 4-Induced 3D Capillary Morphogenesis Correlates to Stabilization of Endothelial Adherens Junctions and Restriction of VEGF-Induced Sprouting Biomedicines angiopoietin-like 4 vascular endothelial growth factor angiogenesis adherens junction in vitro 3D model vascularization |
| title | Angiopoietin-like 4-Induced 3D Capillary Morphogenesis Correlates to Stabilization of Endothelial Adherens Junctions and Restriction of VEGF-Induced Sprouting |
| title_full | Angiopoietin-like 4-Induced 3D Capillary Morphogenesis Correlates to Stabilization of Endothelial Adherens Junctions and Restriction of VEGF-Induced Sprouting |
| title_fullStr | Angiopoietin-like 4-Induced 3D Capillary Morphogenesis Correlates to Stabilization of Endothelial Adherens Junctions and Restriction of VEGF-Induced Sprouting |
| title_full_unstemmed | Angiopoietin-like 4-Induced 3D Capillary Morphogenesis Correlates to Stabilization of Endothelial Adherens Junctions and Restriction of VEGF-Induced Sprouting |
| title_short | Angiopoietin-like 4-Induced 3D Capillary Morphogenesis Correlates to Stabilization of Endothelial Adherens Junctions and Restriction of VEGF-Induced Sprouting |
| title_sort | angiopoietin like 4 induced 3d capillary morphogenesis correlates to stabilization of endothelial adherens junctions and restriction of vegf induced sprouting |
| topic | angiopoietin-like 4 vascular endothelial growth factor angiogenesis adherens junction in vitro 3D model vascularization |
| url | https://www.mdpi.com/2227-9059/10/2/206 |
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