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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">EMILIN1/α9β1 Integrin Interaction Is Crucial in Lymphatic Valve Formation and Maintenance</title>
<author><name sortKey="Danussi, Carla" sort="Danussi, Carla" uniqKey="Danussi C" first="Carla" last="Danussi">Carla Danussi</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Del Bel Belluz, Lisa" sort="Del Bel Belluz, Lisa" uniqKey="Del Bel Belluz L" first="Lisa" last="Del Bel Belluz">Lisa Del Bel Belluz</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pivetta, Eliana" sort="Pivetta, Eliana" uniqKey="Pivetta E" first="Eliana" last="Pivetta">Eliana Pivetta</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Modica, Teresa Maria Elisa" sort="Modica, Teresa Maria Elisa" uniqKey="Modica T" first="Teresa Maria Elisa" last="Modica">Teresa Maria Elisa Modica</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Muro, Andres" sort="Muro, Andres" uniqKey="Muro A" first="Andres" last="Muro">Andres Muro</name>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wassermann, Bruna" sort="Wassermann, Bruna" uniqKey="Wassermann B" first="Bruna" last="Wassermann">Bruna Wassermann</name>
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</affiliation>
</author>
<author><name sortKey="Doliana, Roberto" sort="Doliana, Roberto" uniqKey="Doliana R" first="Roberto" last="Doliana">Roberto Doliana</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sabatelli, Patrizia" sort="Sabatelli, Patrizia" uniqKey="Sabatelli P" first="Patrizia" last="Sabatelli">Patrizia Sabatelli</name>
<affiliation><nlm:aff id="aff3"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff4"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Colombatti, Alfonso" sort="Colombatti, Alfonso" uniqKey="Colombatti A" first="Alfonso" last="Colombatti">Alfonso Colombatti</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff5"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff6"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Spessotto, Paola" sort="Spessotto, Paola" uniqKey="Spessotto P" first="Paola" last="Spessotto">Paola Spessotto</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">24019067</idno>
<idno type="pmc">3838180</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3838180</idno>
<idno type="RBID">PMC:3838180</idno>
<idno type="doi">10.1128/MCB.00872-13</idno>
<date when="2013">2013</date>
<idno type="wicri:Area/Pmc/Corpus">003088</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003088</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">EMILIN1/α9β1 Integrin Interaction Is Crucial in Lymphatic Valve Formation and Maintenance</title>
<author><name sortKey="Danussi, Carla" sort="Danussi, Carla" uniqKey="Danussi C" first="Carla" last="Danussi">Carla Danussi</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Del Bel Belluz, Lisa" sort="Del Bel Belluz, Lisa" uniqKey="Del Bel Belluz L" first="Lisa" last="Del Bel Belluz">Lisa Del Bel Belluz</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pivetta, Eliana" sort="Pivetta, Eliana" uniqKey="Pivetta E" first="Eliana" last="Pivetta">Eliana Pivetta</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Modica, Teresa Maria Elisa" sort="Modica, Teresa Maria Elisa" uniqKey="Modica T" first="Teresa Maria Elisa" last="Modica">Teresa Maria Elisa Modica</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Muro, Andres" sort="Muro, Andres" uniqKey="Muro A" first="Andres" last="Muro">Andres Muro</name>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wassermann, Bruna" sort="Wassermann, Bruna" uniqKey="Wassermann B" first="Bruna" last="Wassermann">Bruna Wassermann</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Doliana, Roberto" sort="Doliana, Roberto" uniqKey="Doliana R" first="Roberto" last="Doliana">Roberto Doliana</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sabatelli, Patrizia" sort="Sabatelli, Patrizia" uniqKey="Sabatelli P" first="Patrizia" last="Sabatelli">Patrizia Sabatelli</name>
<affiliation><nlm:aff id="aff3"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff4"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Colombatti, Alfonso" sort="Colombatti, Alfonso" uniqKey="Colombatti A" first="Alfonso" last="Colombatti">Alfonso Colombatti</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff5"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff6"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Spessotto, Paola" sort="Spessotto, Paola" uniqKey="Spessotto P" first="Paola" last="Spessotto">Paola Spessotto</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Molecular and Cellular Biology</title>
<idno type="ISSN">0270-7306</idno>
<idno type="eISSN">1098-5549</idno>
<imprint><date when="2013">2013</date>
</imprint>
</series>
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<front><div type="abstract" xml:lang="en"><p>Lymphatic vasculature plays a crucial role in the maintenance of tissue interstitial fluid balance. The role of functional collecting lymphatic vessels in lymph transport has been recently highlighted in pathologies leading to lymphedema, for which treatments are currently unavailable. Intraluminal valves are of paramount importance in this process. However, valve formation and maturation have not been entirely elucidated yet, in particular, the role played by the extracellular matrix (ECM). We hypothesized that EMILIN1, an ECM multidomain glycoprotein, regulates lymphatic valve formation and maintenance. Using a mouse knockout model, we show that in the absence of EMILIN1, mice exhibit defects in lymphatic valve structure and in lymph flow. By applying morphometric <italic>in vitro</italic>
and <italic>in vivo</italic>
functional assays, we conclude that this impaired phenotype depends on the lack of α9β1 integrin engagement, the specific lymphatic endothelial cell receptor for EMILIN1, and the ensuing derangement of cell proliferation and migration. Our data demonstrate a fundamental role for EMILIN1-integrin α9 interaction in lymphatic vasculature, especially in lymphatic valve formation and maintenance, and underline the importance of this ECM component in displaying a regulatory function in proliferation and acting as a “guiding” molecule in migration of lymphatic endothelial cells.</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">Mol Cell Biol</journal-id>
<journal-id journal-id-type="iso-abbrev">Mol. Cell. Biol</journal-id>
<journal-id journal-id-type="hwp">mcb</journal-id>
<journal-id journal-id-type="pmc">mcb</journal-id>
<journal-id journal-id-type="publisher-id">MCB</journal-id>
<journal-title-group><journal-title>Molecular and Cellular Biology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0270-7306</issn>
<issn pub-type="epub">1098-5549</issn>
<publisher><publisher-name>American Society for Microbiology</publisher-name>
<publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">24019067</article-id>
<article-id pub-id-type="pmc">3838180</article-id>
<article-id pub-id-type="publisher-id">00872-13</article-id>
<article-id pub-id-type="doi">10.1128/MCB.00872-13</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Articles</subject>
</subj-group>
</article-categories>
<title-group><article-title>EMILIN1/α9β1 Integrin Interaction Is Crucial in Lymphatic Valve Formation and Maintenance</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Danussi</surname>
<given-names>Carla</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="author-notes" rid="fn1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Del Bel Belluz</surname>
<given-names>Lisa</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pivetta</surname>
<given-names>Eliana</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Modica</surname>
<given-names>Teresa Maria Elisa</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Muro</surname>
<given-names>Andres</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wassermann</surname>
<given-names>Bruna</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Doliana</surname>
<given-names>Roberto</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sabatelli</surname>
<given-names>Patrizia</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>c</sup>
</xref>
<xref ref-type="aff" rid="aff4"><sup>d</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Colombatti</surname>
<given-names>Alfonso</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff5"><sup>e</sup>
</xref>
<xref ref-type="aff" rid="aff6"><sup>f</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Spessotto</surname>
<given-names>Paola</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<aff id="aff1">Experimental Oncology 2, CRO, IRCCS, National Cancer Institute, Aviano (PN), Italy<label>a</label>
</aff>
<aff id="aff2">International Centre for Genetic Engineering and Biotechnology, Trieste, Italy<label>b</label>
</aff>
<aff id="aff3">CNR-National Research Council of Italy, IGM-IOR, Bologna, Italy<label>c</label>
</aff>
<aff id="aff4">SC Laboratory of Muscoloskeletal Cell Biology, IOR, Bologna, Italy<label>d</label>
</aff>
<aff id="aff5">Department of Medical and Biomedical Sciences, University of Udine, Udine, Italy<label>e</label>
</aff>
<aff id="aff6">MATI (Microgravity, Ageing, Training, Immobility) Excellence Center, University of Udine, Udine, Italy<label>f</label>
</aff>
</contrib-group>
<author-notes><corresp id="cor1">Address correspondence to Paola Spessotto, <email>pspessotto@cro.it</email>
.</corresp>
<fn id="fn1" fn-type="present-address"><label>*</label>
<p>Present address: Carla Danussi, Institute for Cancer Genetics, Columbia University Medical Center, New York, New York, USA.</p>
</fn>
<fn fn-type="equal"><p>C.D. and L.D.B.B. contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><month>11</month>
<year>2013</year>
</pub-date>
<volume>33</volume>
<issue>22</issue>
<fpage>4381</fpage>
<lpage>4394</lpage>
<history><date date-type="received"><day>8</day>
<month>7</month>
<year>2013</year>
</date>
<date date-type="rev-request"><day>18</day>
<month>8</month>
<year>2013</year>
</date>
<date date-type="accepted"><day>3</day>
<month>9</month>
<year>2013</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2013, American Society for Microbiology. All Rights Reserved.</copyright-statement>
<copyright-year>2013</copyright-year>
<copyright-holder>American Society for Microbiology</copyright-holder>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zmb02213004381.pdf"></self-uri>
<abstract><p>Lymphatic vasculature plays a crucial role in the maintenance of tissue interstitial fluid balance. The role of functional collecting lymphatic vessels in lymph transport has been recently highlighted in pathologies leading to lymphedema, for which treatments are currently unavailable. Intraluminal valves are of paramount importance in this process. However, valve formation and maturation have not been entirely elucidated yet, in particular, the role played by the extracellular matrix (ECM). We hypothesized that EMILIN1, an ECM multidomain glycoprotein, regulates lymphatic valve formation and maintenance. Using a mouse knockout model, we show that in the absence of EMILIN1, mice exhibit defects in lymphatic valve structure and in lymph flow. By applying morphometric <italic>in vitro</italic>
and <italic>in vivo</italic>
functional assays, we conclude that this impaired phenotype depends on the lack of α9β1 integrin engagement, the specific lymphatic endothelial cell receptor for EMILIN1, and the ensuing derangement of cell proliferation and migration. Our data demonstrate a fundamental role for EMILIN1-integrin α9 interaction in lymphatic vasculature, especially in lymphatic valve formation and maintenance, and underline the importance of this ECM component in displaying a regulatory function in proliferation and acting as a “guiding” molecule in migration of lymphatic endothelial cells.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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