Angiopoietin 2 regulates the transformation and integrity of lymphatic endothelial cell junctions
Identifieur interne : 001D53 ( Pmc/Checkpoint ); précédent : 001D52; suivant : 001D54Angiopoietin 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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PMC:4102766Le document en format XML
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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. 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wicri:step="Checkpoint">001D53</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Angiopoietin 2 regulates the transformation and integrity of lymphatic endothelial cell junctions</title><author><name sortKey="Zheng, Wei" sort="Zheng, Wei" uniqKey="Zheng W" first="Wei" last="Zheng">Wei Zheng</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="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><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Genes Dev</journal-id><journal-id journal-id-type="iso-abbrev">Genes Dev</journal-id><journal-id journal-id-type="publisher-id">GAD</journal-id><journal-title-group><journal-title>Genes & Development</journal-title></journal-title-group><issn pub-type="ppub">0890-9369</issn><issn pub-type="epub">1549-5477</issn><publisher><publisher-name>Cold Spring Harbor Laboratory Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25030698</article-id><article-id pub-id-type="pmc">4102766</article-id><article-id pub-id-type="medline">8711660</article-id><article-id pub-id-type="doi">10.1101/gad.237677.114</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Paper</subject></subj-group></article-categories><title-group><article-title>Angiopoietin 2 regulates the transformation and integrity of lymphatic endothelial cell junctions</article-title><alt-title alt-title-type="left-running">Zheng et al.</alt-title><alt-title alt-title-type="right-running">ANG2 regulates LEC junctions</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Zheng</surname><given-names>Wei</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Nurmi</surname><given-names>Harri</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="author-notes" rid="fn1">11</xref></contrib><contrib contrib-type="author"><name><surname>Appak</surname><given-names>Sila</given-names></name><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="author-notes" rid="fn1">11</xref></contrib><contrib contrib-type="author"><name><surname>Sabine</surname><given-names>Amélie</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Bovay</surname><given-names>Esther</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Korhonen</surname><given-names>Emilia A.</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Orsenigo</surname><given-names>Fabrizio</given-names></name><xref ref-type="aff" rid="aff6">6</xref><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Lohela</surname><given-names>Marja</given-names></name><xref ref-type="aff" rid="aff8">8</xref></contrib><contrib contrib-type="author"><name><surname>D’Amico</surname><given-names>Gabriela</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Holopainen</surname><given-names>Tanja</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Leow</surname><given-names>Ching Ching</given-names></name><xref ref-type="aff" rid="aff9">9</xref></contrib><contrib contrib-type="author"><name><surname>Dejana</surname><given-names>Elisabetta</given-names></name><xref ref-type="aff" rid="aff6">6</xref><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Petrova</surname><given-names>Tatiana V.</given-names></name><xref ref-type="aff" rid="aff5">5</xref><xref ref-type="aff" rid="aff10">10</xref></contrib><contrib contrib-type="author"><name><surname>Augustin</surname><given-names>Hellmut G.</given-names></name><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Alitalo</surname><given-names>Kari</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="corresp" rid="cor1">12</xref></contrib><aff id="aff1"><label>1</label>Wihuri Research Institute,</aff><aff id="aff2"><label>2</label>Translational Cancer Biology Program, University of Helsinki, Helsinki 00014, Finland;</aff><aff id="aff3"><label>3</label>Division of Vascular Oncology and Metastasis, German Cancer Research Center Heidelberg, Heidelberg 69120, Germany;</aff><aff id="aff4"><label>4</label>Department of Vascular Biology and Tumor Angiogenesis, Heidelberg University, Mannheim 68167, Germany;</aff><aff id="aff5"><label>5</label>Department of Oncology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Epalinges CH-1066, Switzerland;</aff><aff id="aff6"><label>6</label>FIRC Institute of Molecular Oncology, Milan 20139, Italy;</aff><aff id="aff7"><label>7</label>Department of Biotechnological and Biomolecular Sciences, University of Milan, Milan 20129, Italy;</aff><aff id="aff8"><label>8</label>Biomedicum Imaging Unit, Biomedicum Helsinki, University of Helsinki, Helsinki 00014, Finland;</aff><aff id="aff9"><label>9</label>MedImmune, Gaithersburg, Maryland 20878, USA;</aff><aff id="aff10"><label>10</label>Swiss Institute for Cancer Research, École Polytechnique Fédérale de Lausanne, Lausanne CH-1066, Switzerland</aff></contrib-group><author-notes><fn id="fn1"><label>11</label><p>These authors contributed equally to this work.</p></fn><corresp id="cor1"><label>12</label>Corresponding author E-mail <email xlink:type="simple">kari.alitalo@helsinki.fi</email></corresp></author-notes><pub-date pub-type="ppub"><day>15</day><month>7</month><year>2014</year></pub-date><volume>28</volume><issue>14</issue><fpage>1592</fpage><lpage>1603</lpage><history><date date-type="received"><day>7</day><month>1</month><year>2014</year></date><date date-type="accepted"><day>9</day><month>6</month><year>2014</year></date></history><permissions><copyright-statement><ext-link ext-link-type="uri" xlink:href="http://genesdev.cshlp.org/site/misc/terms.xhtml">© 2014 Zheng et al.; Published by Cold Spring Harbor Laboratory Press</ext-link></copyright-statement><copyright-year>2014</copyright-year><license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/"><license-p>This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see <ext-link ext-link-type="uri" xlink:href="http://genesdev.cshlp.org/site/misc/terms.xhtml">http://genesdev.cshlp.org/site/misc/terms.xhtml</ext-link>). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</ext-link>.</license-p></license></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="1592.pdf"></self-uri><abstract abstract-type="precis"><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></abstract><abstract><p>Primitive lymphatic vessels are remodeled into functionally specialized initial and collecting lymphatics during development. Lymphatic endothelial cell (LEC) junctions in initial lymphatics transform from a zipper-like to a button-like pattern during collecting vessel development, but what regulates this process is largely unknown. Angiopoietin 2 (<italic>Ang2</italic>) deficiency leads to abnormal lymphatic vessels. Here we found that an ANG2-blocking antibody inhibited embryonic lymphangiogenesis, whereas endothelium-specific ANG2 overexpression induced lymphatic hyperplasia. ANG2 inhibition blocked VE-cadherin phosphorylation at tyrosine residue 685 and the concomitant formation of button-like junctions in initial lymphatics. The defective junctions were associated with impaired lymph uptake. In collecting lymphatics, adherens junctions were disrupted, and the vessels leaked upon ANG2 blockade or gene deletion. ANG2 inhibition also 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></abstract><kwd-group><kwd>angiopoietin 2</kwd><kwd>lymphatic</kwd><kwd>VE-cadherin</kwd><kwd>junction</kwd></kwd-group><counts><page-count count="12"></page-count></counts></article-meta></front></pmc><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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