Pathological lymphangiogenesis is modulated by galectin-8-dependent crosstalk between podoplanin and integrin-associated VEGFR-3
Identifieur interne : 000D06 ( Main/Exploration ); précédent : 000D05; suivant : 000D07Pathological lymphangiogenesis is modulated by galectin-8-dependent crosstalk between podoplanin and integrin-associated VEGFR-3
Auteurs : Wei-Sheng Chen [États-Unis] ; Zhiyi Cao [États-Unis] ; Satoshi Sugaya [États-Unis] ; Maria J. Lopez [États-Unis] ; Victor G. Sendra [États-Unis] ; Nora Laver [États-Unis] ; Hakon Leffler [Suède] ; Ulf J. Nilsson [Suède] ; Jianxin Fu [États-Unis] ; Jianhua Song [États-Unis] ; Lijun Xia [États-Unis] ; Pedram Hamrah [États-Unis] ; Noorjahan Panjwani [États-Unis]Source :
- Nature Communications [ 2041-1723 ] ; 2016.
Abstract
Lymphangiogenesis plays a pivotal role in diverse pathological conditions. Here, we demonstrate that a carbohydrate-binding protein, galectin-8, promotes pathological lymphangiogenesis. Galectin-8 is markedly upregulated in inflamed human and mouse corneas, and galectin-8 inhibitors reduce inflammatory lymphangiogenesis. In the mouse model of corneal allogeneic transplantation, galectin-8-induced lymphangiogenesis is associated with an increased rate of corneal graft rejection. Further, in the murine model of herpes simplex virus keratitis, corneal pathology and lymphangiogenesis are ameliorated in
Url:
DOI: 10.1038/ncomms11302
PubMed: 27066737
PubMed Central: 4832077
Affiliations:
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Nilsson</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Centre for Analysis and Synthesis, Department of Chemistry, Lund University</institution>, Lund SE-22100,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Fu, Jianxin" sort="Fu, Jianxin" uniqKey="Fu J" first="Jianxin" last="Fu">Jianxin Fu</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation</institution>, Oklahoma City, Oklahoma 73104,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center</institution>, Oklahoma City, Oklahoma 73104,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Song, Jianhua" sort="Song, Jianhua" uniqKey="Song J" first="Jianhua" last="Song">Jianhua Song</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation</institution>, Oklahoma City, Oklahoma 73104,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center</institution>, Oklahoma City, Oklahoma 73104,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Xia, Lijun" sort="Xia, Lijun" uniqKey="Xia L" first="Lijun" last="Xia">Lijun Xia</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation</institution>, Oklahoma City, Oklahoma 73104,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center</institution>, Oklahoma City, Oklahoma 73104,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hamrah, Pedram" sort="Hamrah, Pedram" uniqKey="Hamrah P" first="Pedram" last="Hamrah">Pedram Hamrah</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>New England Eye Center/Department of Ophthalmology, Tufts University</institution>, Boston, Massachusetts 02111,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Panjwani, Noorjahan" sort="Panjwani, Noorjahan" uniqKey="Panjwani N" first="Noorjahan" last="Panjwani">Noorjahan Panjwani</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University</institution>, Boston, Massachusetts 02111,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>New England Eye Center/Department of Ophthalmology, Tufts University</institution>, Boston, Massachusetts 02111,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Department of Developmental, Molecular and Chemical Biology, Tufts University</institution>, Boston, Massachusetts 02111,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Lymphangiogenesis plays a pivotal role in diverse pathological conditions. Here, we demonstrate that a carbohydrate-binding protein, galectin-8, promotes pathological lymphangiogenesis. Galectin-8 is markedly upregulated in inflamed human and mouse corneas, and galectin-8 inhibitors reduce inflammatory lymphangiogenesis. In the mouse model of corneal allogeneic transplantation, galectin-8-induced lymphangiogenesis is associated with an increased rate of corneal graft rejection. Further, in the murine model of herpes simplex virus keratitis, corneal pathology and lymphangiogenesis are ameliorated in <italic>Lgals8</italic><sup>−/−</sup> mice. Mechanistically, VEGF-C-induced lymphangiogenesis is significantly reduced in the <italic>Lgals8</italic><sup>−/−</sup> and <italic>Pdpn</italic><sup>−/−</sup> mice; likewise, galectin-8-induced lymphangiogenesis is reduced in <italic>Pdpn</italic><sup>−/−</sup> mice. Interestingly, knockdown of VEGFR-3 does not affect galectin-8-mediated lymphatic endothelial cell (LEC) sprouting. Instead, inhibiting integrins α1β1 and α5β1 curtails both galectin-8- and VEGF-C-mediated LEC sprouting. Together, this study uncovers a unique molecular mechanism of lymphangiogenesis in which galectin-8-dependent crosstalk among VEGF-C, podoplanin and integrin pathways plays a key role.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Kerjaschki, D" uniqKey="Kerjaschki D">D. Kerjaschki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aspelund, A" uniqKey="Aspelund A">A. Aspelund</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dietrich, T" uniqKey="Dietrich T">T. Dietrich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goyal, S" uniqKey="Goyal S">S. Goyal</name></author><author><name sortKey="Chauhan, S K" uniqKey="Chauhan S">S. K. Chauhan</name></author><author><name sortKey="Dana, R" uniqKey="Dana R">R. 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Cursiefen</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Suède</li><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Chen, Wei Sheng" sort="Chen, Wei Sheng" uniqKey="Chen W" first="Wei-Sheng" last="Chen">Wei-Sheng Chen</name></noRegion><name sortKey="Cao, Zhiyi" sort="Cao, Zhiyi" uniqKey="Cao Z" first="Zhiyi" last="Cao">Zhiyi Cao</name><name sortKey="Chen, Wei Sheng" sort="Chen, Wei Sheng" uniqKey="Chen W" first="Wei-Sheng" last="Chen">Wei-Sheng Chen</name><name sortKey="Fu, Jianxin" sort="Fu, Jianxin" uniqKey="Fu J" first="Jianxin" last="Fu">Jianxin Fu</name><name sortKey="Fu, Jianxin" sort="Fu, Jianxin" uniqKey="Fu J" first="Jianxin" last="Fu">Jianxin Fu</name><name sortKey="Hamrah, Pedram" sort="Hamrah, Pedram" uniqKey="Hamrah P" first="Pedram" last="Hamrah">Pedram Hamrah</name><name sortKey="Laver, Nora" sort="Laver, Nora" uniqKey="Laver N" first="Nora" last="Laver">Nora Laver</name><name sortKey="Lopez, Maria J" sort="Lopez, Maria J" uniqKey="Lopez M" first="Maria J." last="Lopez">Maria J. Lopez</name><name sortKey="Panjwani, Noorjahan" sort="Panjwani, Noorjahan" uniqKey="Panjwani N" first="Noorjahan" last="Panjwani">Noorjahan Panjwani</name><name sortKey="Panjwani, Noorjahan" sort="Panjwani, Noorjahan" uniqKey="Panjwani N" first="Noorjahan" last="Panjwani">Noorjahan Panjwani</name><name sortKey="Panjwani, Noorjahan" sort="Panjwani, Noorjahan" uniqKey="Panjwani N" first="Noorjahan" last="Panjwani">Noorjahan Panjwani</name><name sortKey="Sendra, Victor G" sort="Sendra, Victor G" uniqKey="Sendra V" first="Victor G." last="Sendra">Victor G. Sendra</name><name sortKey="Song, Jianhua" sort="Song, Jianhua" uniqKey="Song J" first="Jianhua" last="Song">Jianhua Song</name><name sortKey="Song, Jianhua" sort="Song, Jianhua" uniqKey="Song J" first="Jianhua" last="Song">Jianhua Song</name><name sortKey="Sugaya, Satoshi" sort="Sugaya, Satoshi" uniqKey="Sugaya S" first="Satoshi" last="Sugaya">Satoshi Sugaya</name><name sortKey="Xia, Lijun" sort="Xia, Lijun" uniqKey="Xia L" first="Lijun" last="Xia">Lijun Xia</name><name sortKey="Xia, Lijun" sort="Xia, Lijun" uniqKey="Xia L" first="Lijun" last="Xia">Lijun Xia</name></country><country name="Suède"><noRegion><name sortKey="Leffler, Hakon" sort="Leffler, Hakon" uniqKey="Leffler H" first="Hakon" last="Leffler">Hakon Leffler</name></noRegion><name sortKey="Nilsson, Ulf J" sort="Nilsson, Ulf J" uniqKey="Nilsson U" first="Ulf J." last="Nilsson">Ulf J. Nilsson</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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