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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genes regulating lymphangiogenesis control venous valve formation and maintenance in mice</title><author><name sortKey="Bazigou, Eleni" sort="Bazigou, Eleni" uniqKey="Bazigou E" first="Eleni" last="Bazigou">Eleni Bazigou</name><affiliation><nlm:aff id="JCI58050">Lymphatic Development Laboratory, Cancer Research UK London Research Institute, London, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Lyons, Oliver T A" sort="Lyons, Oliver T A" uniqKey="Lyons O" first="Oliver T. A." last="Lyons">Oliver T. A. Lyons</name><affiliation><nlm:aff id="JCI58050">Academic Department of Surgery, Cardiovascular Division, Kings College London, BHF Centre of Research Excellence and NIHR Biomedical Research Centre at King’s Health Partners, St Thomas’ Hospital, London, United Kingdom.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI58050">Division of Biomedical Sciences, St George’s, University of London, Cranmer Terrace, London, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Smith, Alberto" sort="Smith, Alberto" uniqKey="Smith A" first="Alberto" last="Smith">Alberto Smith</name><affiliation><nlm:aff id="JCI58050">Academic Department of Surgery, Cardiovascular Division, Kings College London, BHF Centre of Research Excellence and NIHR Biomedical Research Centre at King’s Health Partners, St Thomas’ Hospital, London, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Venn, Graham E" sort="Venn, Graham E" uniqKey="Venn G" first="Graham E." last="Venn">Graham E. Venn</name><affiliation><nlm:aff id="JCI58050">Cardiothoracic Surgery, St Thomas’ Hospital, King’s Health Partners, London, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Cope, Celia" sort="Cope, Celia" uniqKey="Cope C" first="Celia" last="Cope">Celia Cope</name><affiliation><nlm:aff id="JCI58050">Division of Biomedical Sciences, St George’s, University of London, Cranmer Terrace, London, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Brown, Nigel A" sort="Brown, Nigel A" uniqKey="Brown N" first="Nigel A." last="Brown">Nigel A. Brown</name><affiliation><nlm:aff id="JCI58050">Division of Biomedical Sciences, St George’s, University of London, Cranmer Terrace, London, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Makinen, Taija" sort="Makinen, Taija" uniqKey="Makinen T" first="Taija" last="Makinen">Taija Makinen</name><affiliation><nlm:aff id="JCI58050">Lymphatic Development Laboratory, Cancer Research UK London Research Institute, London, United Kingdom.</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21765212</idno><idno type="pmc">3223924</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223924</idno><idno type="RBID">PMC:3223924</idno><idno type="doi">10.1172/JCI58050</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">002F32</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002F32</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genes regulating lymphangiogenesis control venous valve formation and maintenance in mice</title><author><name sortKey="Bazigou, Eleni" sort="Bazigou, Eleni" uniqKey="Bazigou E" first="Eleni" last="Bazigou">Eleni Bazigou</name><affiliation><nlm:aff id="JCI58050">Lymphatic Development Laboratory, Cancer Research UK London Research Institute, London, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Lyons, Oliver T A" sort="Lyons, Oliver T A" uniqKey="Lyons O" first="Oliver T. A." last="Lyons">Oliver T. A. Lyons</name><affiliation><nlm:aff id="JCI58050">Academic Department of Surgery, Cardiovascular Division, Kings College London, BHF Centre of Research Excellence and NIHR Biomedical Research Centre at King’s Health Partners, St Thomas’ Hospital, London, United Kingdom.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI58050">Division of Biomedical Sciences, St George’s, University of London, Cranmer Terrace, London, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Smith, Alberto" sort="Smith, Alberto" uniqKey="Smith A" first="Alberto" last="Smith">Alberto Smith</name><affiliation><nlm:aff id="JCI58050">Academic Department of Surgery, Cardiovascular Division, Kings College London, BHF Centre of Research Excellence and NIHR Biomedical Research Centre at King’s Health Partners, St Thomas’ Hospital, London, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Venn, Graham E" sort="Venn, Graham E" uniqKey="Venn G" first="Graham E." last="Venn">Graham E. Venn</name><affiliation><nlm:aff id="JCI58050">Cardiothoracic Surgery, St Thomas’ Hospital, King’s Health Partners, London, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Cope, Celia" sort="Cope, Celia" uniqKey="Cope C" first="Celia" last="Cope">Celia Cope</name><affiliation><nlm:aff id="JCI58050">Division of Biomedical Sciences, St George’s, University of London, Cranmer Terrace, London, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Brown, Nigel A" sort="Brown, Nigel A" uniqKey="Brown N" first="Nigel A." last="Brown">Nigel A. Brown</name><affiliation><nlm:aff id="JCI58050">Division of Biomedical Sciences, St George’s, University of London, Cranmer Terrace, London, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Makinen, Taija" sort="Makinen, Taija" uniqKey="Makinen T" first="Taija" last="Makinen">Taija Makinen</name><affiliation><nlm:aff id="JCI58050">Lymphatic Development Laboratory, Cancer Research UK London Research Institute, London, United Kingdom.</nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Clinical Investigation</title><idno type="ISSN">0021-9738</idno><idno type="eISSN">1558-8238</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Chronic venous disease and venous hypertension are common consequences of valve insufficiency, yet the molecular mechanisms regulating the formation and maintenance of venous valves have not been studied. Here, we provide what we believe to be the first description of venous valve morphogenesis and identify signaling pathways required for the process. The initial stages of valve development were found to involve induction of ephrin-B2, a key marker of arterial identity, by venous endothelial cells. Intriguingly, developing and mature venous valves also expressed a repertoire of proteins, including prospero-related homeobox 1 (Prox1), Vegfr3, and integrin-α9, previously characterized as specific and critical regulators of lymphangiogenesis. Using global and venous valve–selective knockout mice, we further demonstrate the requirement of ephrin-B2 and integrin-α9 signaling for the development and maintenance of venous valves. Our findings therefore identified molecular regulators of venous valve development and maintenance and highlighted the involvement of common morphogenetic processes and signaling pathways in controlling valve formation in veins and lymphatic vessels. Unexpectedly, we found that venous valve endothelial cells closely resemble lymphatic (valve) endothelia at the molecular level, suggesting plasticity in the ability of a terminally differentiated endothelial cell to take on a different phenotypic identity.</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">J Clin Invest</journal-id><journal-id journal-id-type="publisher-id">J CLIN INVEST</journal-id><journal-title-group><journal-title>The Journal of Clinical Investigation</journal-title></journal-title-group><issn pub-type="ppub">0021-9738</issn><issn pub-type="epub">1558-8238</issn><publisher><publisher-name>American Society for Clinical Investigation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21765212</article-id><article-id pub-id-type="pmc">3223924</article-id><article-id pub-id-type="publisher-id">58050</article-id><article-id pub-id-type="doi">10.1172/JCI58050</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Genes regulating lymphangiogenesis control venous valve formation and maintenance in mice</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Bazigou</surname><given-names>Eleni</given-names></name><xref ref-type="aff" rid="JCI58050">1</xref></contrib><contrib contrib-type="author"><name><surname>Lyons</surname><given-names>Oliver T.A.</given-names></name><xref ref-type="aff" rid="JCI58050">2</xref><xref ref-type="aff" rid="JCI58050">3</xref></contrib><contrib contrib-type="author"><name><surname>Smith</surname><given-names>Alberto</given-names></name><xref ref-type="aff" rid="JCI58050">2</xref></contrib><contrib contrib-type="author"><name><surname>Venn</surname><given-names>Graham E.</given-names></name><xref ref-type="aff" rid="JCI58050">4</xref></contrib><contrib contrib-type="author"><name><surname>Cope</surname><given-names>Celia</given-names></name><xref ref-type="aff" rid="JCI58050">3</xref></contrib><contrib contrib-type="author"><name><surname>Brown</surname><given-names>Nigel A.</given-names></name><xref ref-type="aff" rid="JCI58050">3</xref></contrib><contrib contrib-type="author"><name><surname>Makinen</surname><given-names>Taija</given-names></name><xref ref-type="aff" rid="JCI58050">1</xref></contrib></contrib-group><aff id="JCI58050"><label>1</label>Lymphatic Development Laboratory, Cancer Research UK London Research Institute, London, United Kingdom.<label>2</label>Academic Department of Surgery, Cardiovascular Division, Kings College London, BHF Centre of Research Excellence and NIHR Biomedical Research Centre at King’s Health Partners, St Thomas’ Hospital, London, United Kingdom.<label>3</label>Division of Biomedical Sciences, St George’s, University of London, Cranmer Terrace, London, United Kingdom.<label>4</label>Cardiothoracic Surgery, St Thomas’ Hospital, King’s Health Partners, London, United Kingdom.</aff><author-notes><corresp>Address correspondence to: Taija Makinen, Lymphatic Development Laboratory, Cancer Research UK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, United Kingdom. Phone: 44.207.269.3459; Fax: 44.207.269.3147; E-mail:
<email>taija.makinen@cancer.org.uk</email>.
</corresp><fn><p><bold>Authorship note:</bold> Eleni Bazigou and Oliver T.A. Lyons contributed equally to this work.
</p></fn></author-notes><pub-date pub-type="epub"><day>18</day><month>7</month><year>2011</year></pub-date><pub-date pub-type="ppub"><day>1</day><month>8</month><year>2011</year></pub-date><pub-date pub-type="pmc-release"><day>18</day><month>7</month><year>2011</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>121</volume><issue>8</issue><fpage>2984</fpage><lpage>2992</lpage><history><date date-type="received"><day>16</day><month>3</month><year>2011</year></date><date date-type="accepted"><day>25</day><month>5</month><year>2011</year></date></history><permissions><copyright-statement>Copyright © 2011, American Society for Clinical Investigation</copyright-statement><copyright-year>2011</copyright-year></permissions><abstract><p>Chronic venous disease and venous hypertension are common consequences of valve insufficiency, yet the molecular mechanisms regulating the formation and maintenance of venous valves have not been studied. Here, we provide what we believe to be the first description of venous valve morphogenesis and identify signaling pathways required for the process. The initial stages of valve development were found to involve induction of ephrin-B2, a key marker of arterial identity, by venous endothelial cells. Intriguingly, developing and mature venous valves also expressed a repertoire of proteins, including prospero-related homeobox 1 (Prox1), Vegfr3, and integrin-α9, previously characterized as specific and critical regulators of lymphangiogenesis. Using global and venous valve–selective knockout mice, we further demonstrate the requirement of ephrin-B2 and integrin-α9 signaling for the development and maintenance of venous valves. Our findings therefore identified molecular regulators of venous valve development and maintenance and highlighted the involvement of common morphogenetic processes and signaling pathways in controlling valve formation in veins and lymphatic vessels. Unexpectedly, we found that venous valve endothelial cells closely resemble lymphatic (valve) endothelia at the molecular level, suggesting plasticity in the ability of a terminally differentiated endothelial cell to take on a different phenotypic identity.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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