Angiopoietin 2 regulates the transformation and integrity of lymphatic endothelial cell junctions
Identifieur interne : 002D54 ( Main/Exploration ); précédent : 002D53; suivant : 002D55Angiopoietin 2 regulates the transformation and integrity of lymphatic endothelial cell junctions
Auteurs : Wei Zheng [Finlande] ; Harri Nurmi [Finlande] ; Sila Appak [Allemagne] ; Amélie Sabine [Suisse] ; Esther Bovay [Suisse] ; Emilia A. Korhonen [Finlande] ; Fabrizio Orsenigo [Italie] ; Marja Lohela [Finlande] ; Gabriela D Mico [Finlande] ; Tanja Holopainen [Finlande] ; Ching Ching Leow [États-Unis] ; Elisabetta Dejana [Italie] ; Tatiana V. Petrova [Suisse] ; Hellmut G. Augustin [Allemagne] ; Kari Alitalo [Finlande]Source :
- Genes & Development [ 0890-9369 ] ; 2014.
Abstract
Lymphatic endothelial cell junctions in lymphatic capillaries transform from a zipper-like to a button-like pattern during development. Here, Zheng et al. found that an Angiopoietin 2 (ANG2)-blocking antibody inhibits embryonic lymphangiogenesis, whereas endothelium-specific ANG2 overexpression induced lymphatic hyperplasia. ANG2 inhibition blocked VE-cadherin phosphorylation and suppressed the onset of lymphatic valve formation and subsequent valve maturation. These data identify ANG2 as the first essential regulator of the functionally important interendothelial cell–cell junctions that form during lymphatic development.
Url:
DOI: 10.1101/gad.237677.114
PubMed: 25030698
PubMed Central: 4102766
Affiliations:
- Allemagne, Finlande, Italie, Suisse, États-Unis
- Bade-Wurtemberg, Canton de Vaud, District de Karlsruhe, Lombardie, Uusimaa
- Heidelberg, Helsinki, Lausanne, Mannheim, Milan
- Université d'Helsinki
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Cancer Biology Program, University of Helsinki, Helsinki 00014</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Nurmi, Harri" sort="Nurmi, Harri" uniqKey="Nurmi H" first="Harri" last="Nurmi">Harri Nurmi</name><affiliation><nlm:aff id="aff1">Wihuri Research Institute,</nlm:aff></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Translational Cancer Biology Program, University of Helsinki, Helsinki 00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Translational Cancer Biology Program, University of Helsinki, Helsinki 00014</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Appak, Sila" sort="Appak, Sila" uniqKey="Appak S" first="Sila" last="Appak">Sila Appak</name><affiliation wicri:level="3"><nlm:aff id="aff3">Division of Vascular Oncology and Metastasis, German Cancer Research Center Heidelberg, Heidelberg 69120, Germany;</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Vascular Oncology and Metastasis, German Cancer Research Center Heidelberg, Heidelberg 69120</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff4">Department of Vascular Biology and Tumor Angiogenesis, Heidelberg University, Mannheim 68167, Germany;</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Vascular Biology and Tumor Angiogenesis, Heidelberg University, Mannheim 68167</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Sabine, Amelie" sort="Sabine, Amelie" uniqKey="Sabine A" first="Amélie" last="Sabine">Amélie Sabine</name><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Oncology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Epalinges CH-1066, Switzerland;</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Oncology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Epalinges CH-1066</wicri:regionArea><wicri:noRegion>Epalinges CH-1066</wicri:noRegion></affiliation></author><author><name sortKey="Bovay, Esther" sort="Bovay, Esther" uniqKey="Bovay E" first="Esther" last="Bovay">Esther Bovay</name><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Oncology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Epalinges CH-1066, Switzerland;</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Oncology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Epalinges CH-1066</wicri:regionArea><wicri:noRegion>Epalinges CH-1066</wicri:noRegion></affiliation></author><author><name sortKey="Korhonen, Emilia A" sort="Korhonen, Emilia A" uniqKey="Korhonen E" first="Emilia A." last="Korhonen">Emilia A. Korhonen</name><affiliation wicri:level="4"><nlm:aff id="aff2">Translational Cancer Biology Program, University of Helsinki, Helsinki 00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Translational Cancer Biology Program, University of Helsinki, Helsinki 00014</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Orsenigo, Fabrizio" sort="Orsenigo, Fabrizio" uniqKey="Orsenigo F" first="Fabrizio" last="Orsenigo">Fabrizio Orsenigo</name><affiliation wicri:level="1"><nlm:aff id="aff6">FIRC Institute of Molecular Oncology, Milan 20139, Italy;</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>FIRC Institute of Molecular Oncology, Milan 20139</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7">Department of Biotechnological and Biomolecular Sciences, University of Milan, Milan 20129, Italy;</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Biotechnological and Biomolecular Sciences, University of Milan, Milan 20129</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Lohela, Marja" sort="Lohela, Marja" uniqKey="Lohela M" first="Marja" last="Lohela">Marja Lohela</name><affiliation wicri:level="4"><nlm:aff id="aff8">Biomedicum Imaging Unit, Biomedicum Helsinki, University of Helsinki, Helsinki 00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Biomedicum Imaging Unit, Biomedicum Helsinki, University of Helsinki, Helsinki 00014</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="D Mico, Gabriela" sort="D Mico, Gabriela" uniqKey="D Mico G" first="Gabriela" last="D Mico">Gabriela D Mico</name><affiliation wicri:level="4"><nlm:aff id="aff2">Translational Cancer Biology Program, University of Helsinki, Helsinki 00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Translational Cancer Biology Program, University of Helsinki, Helsinki 00014</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Holopainen, Tanja" sort="Holopainen, Tanja" uniqKey="Holopainen T" first="Tanja" last="Holopainen">Tanja Holopainen</name><affiliation wicri:level="4"><nlm:aff id="aff2">Translational Cancer Biology Program, University of Helsinki, Helsinki 00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Translational Cancer Biology Program, University of Helsinki, Helsinki 00014</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Leow, Ching Ching" sort="Leow, Ching Ching" uniqKey="Leow C" first="Ching Ching" last="Leow">Ching Ching Leow</name><affiliation wicri:level="1"><nlm:aff id="aff9">MedImmune, Gaithersburg, Maryland 20878, USA;</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>MedImmune, Gaithersburg, Maryland 20878</wicri:regionArea><wicri:noRegion>Maryland 20878</wicri:noRegion></affiliation></author><author><name sortKey="Dejana, Elisabetta" sort="Dejana, Elisabetta" uniqKey="Dejana E" first="Elisabetta" last="Dejana">Elisabetta Dejana</name><affiliation wicri:level="1"><nlm:aff id="aff6">FIRC Institute of Molecular Oncology, Milan 20139, Italy;</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>FIRC Institute of Molecular Oncology, Milan 20139</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7">Department of Biotechnological and Biomolecular Sciences, University of Milan, Milan 20129, Italy;</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Biotechnological and Biomolecular Sciences, University of Milan, Milan 20129</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Petrova, Tatiana V" sort="Petrova, Tatiana V" uniqKey="Petrova T" first="Tatiana V." last="Petrova">Tatiana V. Petrova</name><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Oncology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Epalinges CH-1066, Switzerland;</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Oncology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Epalinges CH-1066</wicri:regionArea><wicri:noRegion>Epalinges CH-1066</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff10">Swiss Institute for Cancer Research, École Polytechnique Fédérale de Lausanne, Lausanne CH-1066, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Swiss Institute for Cancer Research, École Polytechnique Fédérale de Lausanne, Lausanne CH-1066</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Augustin, Hellmut G" sort="Augustin, Hellmut G" uniqKey="Augustin H" first="Hellmut G." last="Augustin">Hellmut G. Augustin</name><affiliation wicri:level="3"><nlm:aff id="aff3">Division of Vascular Oncology and Metastasis, German Cancer Research Center Heidelberg, Heidelberg 69120, Germany;</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Vascular Oncology and Metastasis, German Cancer Research Center Heidelberg, Heidelberg 69120</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff4">Department of Vascular Biology and Tumor Angiogenesis, Heidelberg University, Mannheim 68167, Germany;</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Vascular Biology and Tumor Angiogenesis, Heidelberg University, Mannheim 68167</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><affiliation><nlm:aff id="aff1">Wihuri Research Institute,</nlm:aff><country>Finlande</country><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><orgName type="university">Université d'Helsinki</orgName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Translational Cancer Biology Program, University of Helsinki, Helsinki 00014, Finland;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Translational Cancer Biology Program, University of Helsinki, Helsinki 00014</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><orgName type="university">Université d'Helsinki</orgName></affiliation></author></analytic><series><title level="j">Genes & Development</title><idno type="ISSN">0890-9369</idno><idno type="eISSN">1549-5477</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Lymphatic endothelial cell junctions in lymphatic capillaries transform from a zipper-like to a button-like pattern during development. Here, Zheng et al. found that an Angiopoietin 2 (ANG2)-blocking antibody inhibits embryonic lymphangiogenesis, whereas endothelium-specific ANG2 overexpression induced lymphatic hyperplasia. ANG2 inhibition blocked VE-cadherin phosphorylation and suppressed the onset of lymphatic valve formation and subsequent valve maturation. These data identify ANG2 as the first essential regulator of the functionally important interendothelial cell–cell junctions that form during lymphatic development.</p></div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Finlande</li><li>Italie</li><li>Suisse</li><li>États-Unis</li></country><region><li>Bade-Wurtemberg</li><li>Canton de Vaud</li><li>District de Karlsruhe</li><li>Lombardie</li><li>Uusimaa</li></region><settlement><li>Heidelberg</li><li>Helsinki</li><li>Lausanne</li><li>Mannheim</li><li>Milan</li></settlement><orgName><li>Université d'Helsinki</li></orgName></list><tree><country name="Finlande"><region name="Uusimaa"><name sortKey="Zheng, Wei" sort="Zheng, Wei" uniqKey="Zheng W" first="Wei" last="Zheng">Wei Zheng</name></region><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><name sortKey="D Mico, Gabriela" sort="D Mico, Gabriela" uniqKey="D Mico G" first="Gabriela" last="D Mico">Gabriela D Mico</name><name sortKey="Holopainen, Tanja" sort="Holopainen, Tanja" uniqKey="Holopainen T" first="Tanja" last="Holopainen">Tanja Holopainen</name><name sortKey="Korhonen, Emilia A" sort="Korhonen, Emilia A" uniqKey="Korhonen E" first="Emilia A." last="Korhonen">Emilia A. Korhonen</name><name sortKey="Lohela, Marja" sort="Lohela, Marja" uniqKey="Lohela M" first="Marja" last="Lohela">Marja Lohela</name><name sortKey="Nurmi, Harri" sort="Nurmi, Harri" uniqKey="Nurmi H" first="Harri" last="Nurmi">Harri Nurmi</name></country><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Appak, Sila" sort="Appak, Sila" uniqKey="Appak S" first="Sila" last="Appak">Sila Appak</name></region><name sortKey="Appak, Sila" sort="Appak, Sila" uniqKey="Appak S" first="Sila" last="Appak">Sila Appak</name><name sortKey="Augustin, Hellmut G" sort="Augustin, Hellmut G" uniqKey="Augustin H" first="Hellmut G." last="Augustin">Hellmut G. Augustin</name><name sortKey="Augustin, Hellmut G" sort="Augustin, Hellmut G" uniqKey="Augustin H" first="Hellmut G." last="Augustin">Hellmut G. Augustin</name></country><country name="Suisse"><noRegion><name sortKey="Sabine, Amelie" sort="Sabine, Amelie" uniqKey="Sabine A" first="Amélie" last="Sabine">Amélie Sabine</name></noRegion><name sortKey="Bovay, Esther" sort="Bovay, Esther" uniqKey="Bovay E" first="Esther" last="Bovay">Esther Bovay</name><name sortKey="Petrova, Tatiana V" sort="Petrova, Tatiana V" uniqKey="Petrova T" first="Tatiana V." last="Petrova">Tatiana V. Petrova</name><name sortKey="Petrova, Tatiana V" sort="Petrova, Tatiana V" uniqKey="Petrova T" first="Tatiana V." last="Petrova">Tatiana V. Petrova</name></country><country name="Italie"><region name="Lombardie"><name sortKey="Orsenigo, Fabrizio" sort="Orsenigo, Fabrizio" uniqKey="Orsenigo F" first="Fabrizio" last="Orsenigo">Fabrizio Orsenigo</name></region><name sortKey="Dejana, Elisabetta" sort="Dejana, Elisabetta" uniqKey="Dejana E" first="Elisabetta" last="Dejana">Elisabetta Dejana</name><name sortKey="Dejana, Elisabetta" sort="Dejana, Elisabetta" uniqKey="Dejana E" first="Elisabetta" last="Dejana">Elisabetta Dejana</name><name sortKey="Orsenigo, Fabrizio" sort="Orsenigo, Fabrizio" uniqKey="Orsenigo F" first="Fabrizio" last="Orsenigo">Fabrizio Orsenigo</name></country><country name="États-Unis"><noRegion><name sortKey="Leow, Ching Ching" sort="Leow, Ching Ching" uniqKey="Leow C" first="Ching Ching" last="Leow">Ching Ching Leow</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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