Alternatively spliced VEGF receptor-2 is an essential endogenous inhibitor of lymphatic vessels
Identifieur interne : 006409 ( Main/Exploration ); précédent : 006408; suivant : 006410Alternatively spliced VEGF receptor-2 is an essential endogenous inhibitor of lymphatic vessels
Auteurs : Romulo J. C. Albuquerque [États-Unis] ; Takahiko Hayashi [Japon] ; Won Gil Cho [États-Unis] ; Mark E. Kleinman [États-Unis] ; Sami Dridi [États-Unis] ; Atsunobu Takeda [États-Unis] ; Judit Z. Baffi [États-Unis] ; Kiyoshi Yamada [États-Unis] ; Hiroki Kaneko [États-Unis] ; Martha G. Green [États-Unis] ; Joe Chappell [États-Unis] ; Jörg Wilting [Allemagne] ; Herbert A. Weich [Allemagne] ; Satoru Yamagami [Japon] ; Shiro Amano [Japon] ; Nobuhisa Mizuki [Japon] ; Jonathan S. Alexander [États-Unis] ; Martha L. Peterson [États-Unis] ; Rolf A. Brekken [États-Unis] ; Masanori Hirashima [Japon] ; Seema Capoor [États-Unis] ; Tomohiko Usui [Japon] ; Balamurali K. Ambati [États-Unis] ; Jayakrishna Ambati [États-Unis]Source :
- Nature medicine [ 1078-8956 ] ; 2009.
Descripteurs français
- KwdFr :
- ADN complémentaire (génétique), Animaux, Animaux nouveau-nés, Cornée (), Cornée (croissance et développement), Cornée (métabolisme), Données de séquences moléculaires, Facteur de croissance endothéliale vasculaire de type C (antagonistes et inhibiteurs), Facteur de croissance endothéliale vasculaire de type C (physiologie), Humains, Lymphangiogenèse (génétique), Lymphangiogenèse (physiologie), Récepteur-2 au facteur croissance endothéliale vasculaire (déficit), Récepteur-2 au facteur croissance endothéliale vasculaire (génétique), Récepteur-2 au facteur croissance endothéliale vasculaire (physiologie), Souches mutantes de souris, Souris, Souris de lignée BALB C, Souris de lignée C57BL, Séquence nucléotidique, Vaisseaux lymphatiques (physiologie), Épissage alternatif.
- MESH :
- antagonistes et inhibiteurs : Facteur de croissance endothéliale vasculaire de type C.
- croissance et développement : Cornée.
- déficit : Récepteur-2 au facteur croissance endothéliale vasculaire.
- génétique : ADN complémentaire, Lymphangiogenèse, Récepteur-2 au facteur croissance endothéliale vasculaire.
- métabolisme : Cornée.
- physiologie : Facteur de croissance endothéliale vasculaire de type C, Lymphangiogenèse, Récepteur-2 au facteur croissance endothéliale vasculaire, Vaisseaux lymphatiques.
- Animaux, Animaux nouveau-nés, Cornée, Données de séquences moléculaires, Humains, Souches mutantes de souris, Souris, Souris de lignée BALB C, Souris de lignée C57BL, Séquence nucléotidique, Épissage alternatif.
English descriptors
- KwdEn :
- Alternative Splicing, Animals, Animals, Newborn, Base Sequence, Cornea (blood supply), Cornea (growth & development), Cornea (metabolism), DNA, Complementary (genetics), Humans, Lymphangiogenesis (genetics), Lymphangiogenesis (physiology), Lymphatic Vessels (physiology), Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Mutant Strains, Molecular Sequence Data, Vascular Endothelial Growth Factor C (antagonists & inhibitors), Vascular Endothelial Growth Factor C (physiology), Vascular Endothelial Growth Factor Receptor-2 (deficiency), Vascular Endothelial Growth Factor Receptor-2 (genetics), Vascular Endothelial Growth Factor Receptor-2 (physiology).
- MESH :
- chemical , antagonists & inhibitors : Vascular Endothelial Growth Factor C.
- chemical , deficiency : Vascular Endothelial Growth Factor Receptor-2.
- chemical , genetics : DNA, Complementary, Vascular Endothelial Growth Factor Receptor-2.
- blood supply : Cornea.
- genetics : Lymphangiogenesis.
- growth & development : Cornea.
- metabolism : Cornea.
- physiology : Lymphangiogenesis, Lymphatic Vessels, Vascular Endothelial Growth Factor C, Vascular Endothelial Growth Factor Receptor-2.
- Alternative Splicing, Animals, Animals, Newborn, Base Sequence, Humans, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Mutant Strains, Molecular Sequence Data.
Abstract
Disruption of the precise balance of positive and negative molecular regulators of blood and lymphatic vessels can lead to myriad diseases that affect one in four people worldwide. Although dozens of natural inhibitors of hemangiogenesis have been identified, an endogenous selective inhibitor of lymphatic vessels has not yet been described. We report the existence of a secreted, splice variant of vascular endothelial growth factor receptor-2 (sVegfr-2) that inhibits developmental and reparative lymphangiogenesis by blocking Vegf-c. Tissue-specific loss of sVegfr-2 in mice induced, at birth, spontaneous lymphatic invasion of the normally alymphatic cornea and hyperplasia of skin lymphatics without accompanying changes in blood vasculature. sVegfr-2 inhibited lymphangiogenesis but not hemangiogenesis induced by corneal suture injury or transplantation, enhanced corneal allograft survival, and suppressed lymphangioma cellular proliferation. Naturally occurring sVegfr-2 is a molecular uncoupler of blood and lymphatic vessels whose modulation might have a therapeutic role in lymphatic vascular malformations, transplantation, and potentially in tumor lymphangiogenesis and lymphedema.
Url:
DOI: 10.1038/nm.2018
PubMed: 19668192
PubMed Central: 2882165
Affiliations:
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Le document en format XML
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Green</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation></author><author><name sortKey="Chappell, Joe" sort="Chappell, Joe" uniqKey="Chappell J" first="Joe" last="Chappell">Joe Chappell</name><affiliation wicri:level="1"><nlm:aff id="A4">Department of Plant & Soil Sciences, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Plant & Soil Sciences, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation></author><author><name sortKey="Wilting, Jorg" sort="Wilting, Jorg" uniqKey="Wilting J" first="Jörg" last="Wilting">Jörg Wilting</name><affiliation wicri:level="1"><nlm:aff id="A5">Department of Anatomy and Cell Biology, Georg-August-University, Goettingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Anatomy and Cell Biology, Georg-August-University, Goettingen</wicri:regionArea><wicri:noRegion>Goettingen</wicri:noRegion><wicri:noRegion>Goettingen</wicri:noRegion><wicri:noRegion>Goettingen</wicri:noRegion></affiliation></author><author><name sortKey="Weich, Herbert A" sort="Weich, Herbert A" uniqKey="Weich H" first="Herbert A." last="Weich">Herbert A. Weich</name><affiliation wicri:level="1"><nlm:aff id="A6">Department Gene Regulation and Differentiation, Helmholtz Centre for Infection Research, Braunschweig, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department Gene Regulation and Differentiation, Helmholtz Centre for Infection Research, Braunschweig</wicri:regionArea><wicri:noRegion>Braunschweig</wicri:noRegion><wicri:noRegion>Braunschweig</wicri:noRegion><wicri:noRegion>Braunschweig</wicri:noRegion></affiliation></author><author><name sortKey="Yamagami, Satoru" sort="Yamagami, Satoru" uniqKey="Yamagami S" first="Satoru" last="Yamagami">Satoru Yamagami</name><affiliation wicri:level="1"><nlm:aff id="A7">Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, 113-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, 113-8655</wicri:regionArea><wicri:noRegion>113-8655</wicri:noRegion></affiliation></author><author><name sortKey="Amano, Shiro" sort="Amano, Shiro" uniqKey="Amano S" first="Shiro" last="Amano">Shiro Amano</name><affiliation wicri:level="1"><nlm:aff id="A7">Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, 113-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, 113-8655</wicri:regionArea><wicri:noRegion>113-8655</wicri:noRegion></affiliation></author><author><name sortKey="Mizuki, Nobuhisa" sort="Mizuki, Nobuhisa" uniqKey="Mizuki N" first="Nobuhisa" last="Mizuki">Nobuhisa Mizuki</name><affiliation wicri:level="1"><nlm:aff id="A3">Department of Ophthalmology, Yokohama City University, Yokohama, 221-0044, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Ophthalmology, Yokohama City University, Yokohama, 221-0044</wicri:regionArea><wicri:noRegion>221-0044</wicri:noRegion></affiliation></author><author><name sortKey="Alexander, Jonathan S" sort="Alexander, Jonathan S" uniqKey="Alexander J" first="Jonathan S." last="Alexander">Jonathan S. Alexander</name><affiliation wicri:level="1"><nlm:aff id="A8">Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932</wicri:regionArea><wicri:noRegion>Louisiana 71130-3932</wicri:noRegion></affiliation></author><author><name sortKey="Peterson, Martha L" sort="Peterson, Martha L" uniqKey="Peterson M" first="Martha L." last="Peterson">Martha L. Peterson</name><affiliation wicri:level="1"><nlm:aff id="A9">Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation></author><author><name sortKey="Brekken, Rolf A" sort="Brekken, Rolf A" uniqKey="Brekken R" first="Rolf A." last="Brekken">Rolf A. Brekken</name><affiliation wicri:level="1"><nlm:aff id="A10">Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8593, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8593</wicri:regionArea><wicri:noRegion>Texas 75390-8593</wicri:noRegion></affiliation></author><author><name sortKey="Hirashima, Masanori" sort="Hirashima, Masanori" uniqKey="Hirashima M" first="Masanori" last="Hirashima">Masanori Hirashima</name><affiliation wicri:level="1"><nlm:aff id="A11">Division of Vascular Biology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Vascular Biology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017</wicri:regionArea><wicri:noRegion>Kobe 650-0017</wicri:noRegion></affiliation></author><author><name sortKey="Capoor, Seema" sort="Capoor, Seema" uniqKey="Capoor S" first="Seema" last="Capoor">Seema Capoor</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation></author><author><name sortKey="Usui, Tomohiko" sort="Usui, Tomohiko" uniqKey="Usui T" first="Tomohiko" last="Usui">Tomohiko Usui</name><affiliation wicri:level="1"><nlm:aff id="A7">Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, 113-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, 113-8655</wicri:regionArea><wicri:noRegion>113-8655</wicri:noRegion></affiliation></author><author><name sortKey="Ambati, Balamurali K" sort="Ambati, Balamurali K" uniqKey="Ambati B" first="Balamurali K." last="Ambati">Balamurali K. Ambati</name><affiliation wicri:level="1"><nlm:aff id="A12">Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, Utah 84132</wicri:regionArea><wicri:noRegion>Utah 84132</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A13">Department of Ophthalmology, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, Utah 84148, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, Utah 84148</wicri:regionArea><wicri:noRegion>Utah 84148</wicri:noRegion></affiliation></author><author><name sortKey="Ambati, Jayakrishna" sort="Ambati, Jayakrishna" uniqKey="Ambati J" first="Jayakrishna" last="Ambati">Jayakrishna Ambati</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Department of Physiology, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Physiology, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19668192</idno><idno type="pmc">2882165</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882165</idno><idno type="RBID">PMC:2882165</idno><idno type="doi">10.1038/nm.2018</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">004712</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">004712</idno><idno type="wicri:Area/Pmc/Curation">004711</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">004711</idno><idno type="wicri:Area/Pmc/Checkpoint">003824</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">003824</idno><idno type="wicri:source">PubMed</idno><idno type="wicri:Area/PubMed/Corpus">002D85</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002D85</idno><idno type="wicri:Area/PubMed/Curation">002D85</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002D85</idno><idno type="wicri:Area/PubMed/Checkpoint">002D85</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002D85</idno><idno type="wicri:Area/Ncbi/Merge">003554</idno><idno type="wicri:Area/Ncbi/Curation">003554</idno><idno type="wicri:Area/Ncbi/Checkpoint">003554</idno><idno type="wicri:doubleKey">1078-8956:2009:Albuquerque R:alternatively:spliced:vegf</idno><idno type="wicri:Area/Main/Merge">006487</idno><idno type="wicri:Area/Main/Curation">006409</idno><idno type="wicri:Area/Main/Exploration">006409</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Alternatively spliced VEGF receptor-2 is an essential endogenous inhibitor of lymphatic vessels</title><author><name sortKey="Albuquerque, Romulo J C" sort="Albuquerque, Romulo J C" uniqKey="Albuquerque R" first="Romulo J. C." last="Albuquerque">Romulo J. C. Albuquerque</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Department of Physiology, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Physiology, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation></author><author><name sortKey="Hayashi, Takahiko" sort="Hayashi, Takahiko" uniqKey="Hayashi T" first="Takahiko" last="Hayashi">Takahiko Hayashi</name><affiliation wicri:level="1"><nlm:aff id="A3">Department of Ophthalmology, Yokohama City University, Yokohama, 221-0044, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Ophthalmology, Yokohama City University, Yokohama, 221-0044</wicri:regionArea><wicri:noRegion>221-0044</wicri:noRegion></affiliation></author><author><name sortKey="Cho, Won Gil" sort="Cho, Won Gil" uniqKey="Cho W" first="Won Gil" last="Cho">Won Gil Cho</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation></author><author><name sortKey="Kleinman, Mark E" sort="Kleinman, Mark E" uniqKey="Kleinman M" first="Mark E." last="Kleinman">Mark E. Kleinman</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation></author><author><name sortKey="Dridi, Sami" sort="Dridi, Sami" uniqKey="Dridi S" first="Sami" last="Dridi">Sami Dridi</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation></author><author><name sortKey="Takeda, Atsunobu" sort="Takeda, Atsunobu" uniqKey="Takeda A" first="Atsunobu" last="Takeda">Atsunobu Takeda</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation></author><author><name sortKey="Baffi, Judit Z" sort="Baffi, Judit Z" uniqKey="Baffi J" first="Judit Z." last="Baffi">Judit Z. Baffi</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation></author><author><name sortKey="Yamada, Kiyoshi" sort="Yamada, Kiyoshi" uniqKey="Yamada K" first="Kiyoshi" last="Yamada">Kiyoshi Yamada</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation></author><author><name sortKey="Kaneko, Hiroki" sort="Kaneko, Hiroki" uniqKey="Kaneko H" first="Hiroki" last="Kaneko">Hiroki Kaneko</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation></author><author><name sortKey="Green, Martha G" sort="Green, Martha G" uniqKey="Green M" first="Martha G." last="Green">Martha G. Green</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation></author><author><name sortKey="Chappell, Joe" sort="Chappell, Joe" uniqKey="Chappell J" first="Joe" last="Chappell">Joe Chappell</name><affiliation wicri:level="1"><nlm:aff id="A4">Department of Plant & Soil Sciences, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Plant & Soil Sciences, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation></author><author><name sortKey="Wilting, Jorg" sort="Wilting, Jorg" uniqKey="Wilting J" first="Jörg" last="Wilting">Jörg Wilting</name><affiliation wicri:level="1"><nlm:aff id="A5">Department of Anatomy and Cell Biology, Georg-August-University, Goettingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Anatomy and Cell Biology, Georg-August-University, Goettingen</wicri:regionArea><wicri:noRegion>Goettingen</wicri:noRegion><wicri:noRegion>Goettingen</wicri:noRegion><wicri:noRegion>Goettingen</wicri:noRegion></affiliation></author><author><name sortKey="Weich, Herbert A" sort="Weich, Herbert A" uniqKey="Weich H" first="Herbert A." last="Weich">Herbert A. Weich</name><affiliation wicri:level="1"><nlm:aff id="A6">Department Gene Regulation and Differentiation, Helmholtz Centre for Infection Research, Braunschweig, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department Gene Regulation and Differentiation, Helmholtz Centre for Infection Research, Braunschweig</wicri:regionArea><wicri:noRegion>Braunschweig</wicri:noRegion><wicri:noRegion>Braunschweig</wicri:noRegion><wicri:noRegion>Braunschweig</wicri:noRegion></affiliation></author><author><name sortKey="Yamagami, Satoru" sort="Yamagami, Satoru" uniqKey="Yamagami S" first="Satoru" last="Yamagami">Satoru Yamagami</name><affiliation wicri:level="1"><nlm:aff id="A7">Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, 113-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, 113-8655</wicri:regionArea><wicri:noRegion>113-8655</wicri:noRegion></affiliation></author><author><name sortKey="Amano, Shiro" sort="Amano, Shiro" uniqKey="Amano S" first="Shiro" last="Amano">Shiro Amano</name><affiliation wicri:level="1"><nlm:aff id="A7">Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, 113-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, 113-8655</wicri:regionArea><wicri:noRegion>113-8655</wicri:noRegion></affiliation></author><author><name sortKey="Mizuki, Nobuhisa" sort="Mizuki, Nobuhisa" uniqKey="Mizuki N" first="Nobuhisa" last="Mizuki">Nobuhisa Mizuki</name><affiliation wicri:level="1"><nlm:aff id="A3">Department of Ophthalmology, Yokohama City University, Yokohama, 221-0044, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Ophthalmology, Yokohama City University, Yokohama, 221-0044</wicri:regionArea><wicri:noRegion>221-0044</wicri:noRegion></affiliation></author><author><name sortKey="Alexander, Jonathan S" sort="Alexander, Jonathan S" uniqKey="Alexander J" first="Jonathan S." last="Alexander">Jonathan S. Alexander</name><affiliation wicri:level="1"><nlm:aff id="A8">Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932</wicri:regionArea><wicri:noRegion>Louisiana 71130-3932</wicri:noRegion></affiliation></author><author><name sortKey="Peterson, Martha L" sort="Peterson, Martha L" uniqKey="Peterson M" first="Martha L." last="Peterson">Martha L. Peterson</name><affiliation wicri:level="1"><nlm:aff id="A9">Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation></author><author><name sortKey="Brekken, Rolf A" sort="Brekken, Rolf A" uniqKey="Brekken R" first="Rolf A." last="Brekken">Rolf A. Brekken</name><affiliation wicri:level="1"><nlm:aff id="A10">Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8593, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8593</wicri:regionArea><wicri:noRegion>Texas 75390-8593</wicri:noRegion></affiliation></author><author><name sortKey="Hirashima, Masanori" sort="Hirashima, Masanori" uniqKey="Hirashima M" first="Masanori" last="Hirashima">Masanori Hirashima</name><affiliation wicri:level="1"><nlm:aff id="A11">Division of Vascular Biology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Vascular Biology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017</wicri:regionArea><wicri:noRegion>Kobe 650-0017</wicri:noRegion></affiliation></author><author><name sortKey="Capoor, Seema" sort="Capoor, Seema" uniqKey="Capoor S" first="Seema" last="Capoor">Seema Capoor</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation></author><author><name sortKey="Usui, Tomohiko" sort="Usui, Tomohiko" uniqKey="Usui T" first="Tomohiko" last="Usui">Tomohiko Usui</name><affiliation wicri:level="1"><nlm:aff id="A7">Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, 113-8655, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, 113-8655</wicri:regionArea><wicri:noRegion>113-8655</wicri:noRegion></affiliation></author><author><name sortKey="Ambati, Balamurali K" sort="Ambati, Balamurali K" uniqKey="Ambati B" first="Balamurali K." last="Ambati">Balamurali K. Ambati</name><affiliation wicri:level="1"><nlm:aff id="A12">Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, Utah 84132</wicri:regionArea><wicri:noRegion>Utah 84132</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A13">Department of Ophthalmology, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, Utah 84148, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, Utah 84148</wicri:regionArea><wicri:noRegion>Utah 84148</wicri:noRegion></affiliation></author><author><name sortKey="Ambati, Jayakrishna" sort="Ambati, Jayakrishna" uniqKey="Ambati J" first="Jayakrishna" last="Ambati">Jayakrishna Ambati</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Department of Physiology, University of Kentucky, Lexington, Kentucky 40536, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Physiology, University of Kentucky, Lexington, Kentucky 40536</wicri:regionArea><wicri:noRegion>Kentucky 40536</wicri:noRegion></affiliation></author></analytic><series><title level="j">Nature medicine</title><idno type="ISSN">1078-8956</idno><idno type="eISSN">1546-170X</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alternative Splicing</term><term>Animals</term><term>Animals, Newborn</term><term>Base Sequence</term><term>Cornea (blood supply)</term><term>Cornea (growth & development)</term><term>Cornea (metabolism)</term><term>DNA, Complementary (genetics)</term><term>Humans</term><term>Lymphangiogenesis (genetics)</term><term>Lymphangiogenesis (physiology)</term><term>Lymphatic Vessels (physiology)</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, Inbred C57BL</term><term>Mice, Mutant Strains</term><term>Molecular Sequence Data</term><term>Vascular Endothelial Growth Factor C (antagonists & inhibitors)</term><term>Vascular Endothelial Growth Factor C (physiology)</term><term>Vascular Endothelial Growth Factor Receptor-2 (deficiency)</term><term>Vascular Endothelial Growth Factor Receptor-2 (genetics)</term><term>Vascular Endothelial Growth Factor Receptor-2 (physiology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN complémentaire (génétique)</term><term>Animaux</term><term>Animaux nouveau-nés</term><term>Cornée ()</term><term>Cornée (croissance et développement)</term><term>Cornée (métabolisme)</term><term>Données de séquences moléculaires</term><term>Facteur de croissance endothéliale vasculaire de type C (antagonistes et inhibiteurs)</term><term>Facteur de croissance endothéliale vasculaire de type C (physiologie)</term><term>Humains</term><term>Lymphangiogenèse (génétique)</term><term>Lymphangiogenèse (physiologie)</term><term>Récepteur-2 au facteur croissance endothéliale vasculaire (déficit)</term><term>Récepteur-2 au facteur croissance endothéliale vasculaire (génétique)</term><term>Récepteur-2 au facteur croissance endothéliale vasculaire (physiologie)</term><term>Souches mutantes de souris</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Souris de lignée C57BL</term><term>Séquence nucléotidique</term><term>Vaisseaux lymphatiques (physiologie)</term><term>Épissage alternatif</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Vascular Endothelial Growth Factor C</term></keywords><keywords scheme="MESH" type="chemical" qualifier="deficiency" xml:lang="en"><term>Vascular Endothelial Growth Factor Receptor-2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DNA, Complementary</term><term>Vascular Endothelial Growth Factor Receptor-2</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Facteur de croissance endothéliale vasculaire de type C</term></keywords><keywords scheme="MESH" qualifier="blood supply" xml:lang="en"><term>Cornea</term></keywords><keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Cornée</term></keywords><keywords scheme="MESH" qualifier="déficit" xml:lang="fr"><term>Récepteur-2 au facteur croissance endothéliale vasculaire</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Lymphangiogenesis</term></keywords><keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Cornea</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ADN complémentaire</term><term>Lymphangiogenèse</term><term>Récepteur-2 au facteur croissance endothéliale vasculaire</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Cornea</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cornée</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Facteur de croissance endothéliale vasculaire de type C</term><term>Lymphangiogenèse</term><term>Récepteur-2 au facteur croissance endothéliale vasculaire</term><term>Vaisseaux lymphatiques</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Lymphangiogenesis</term><term>Lymphatic Vessels</term><term>Vascular Endothelial Growth Factor C</term><term>Vascular Endothelial Growth Factor Receptor-2</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Alternative Splicing</term><term>Animals</term><term>Animals, Newborn</term><term>Base Sequence</term><term>Humans</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, Inbred C57BL</term><term>Mice, Mutant Strains</term><term>Molecular Sequence Data</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Animaux nouveau-nés</term><term>Cornée</term><term>Données de séquences moléculaires</term><term>Humains</term><term>Souches mutantes de souris</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Souris de lignée C57BL</term><term>Séquence nucléotidique</term><term>Épissage alternatif</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P2">Disruption of the precise balance of positive and negative molecular regulators of blood and lymphatic vessels can lead to myriad diseases that affect one in four people worldwide. Although dozens of natural inhibitors of hemangiogenesis have been identified, an endogenous selective inhibitor of lymphatic vessels has not yet been described. We report the existence of a secreted, splice variant of vascular endothelial growth factor receptor-2 (sVegfr-2) that inhibits developmental and reparative lymphangiogenesis by blocking Vegf-c. Tissue-specific loss of sVegfr-2 in mice induced, at birth, spontaneous lymphatic invasion of the normally alymphatic cornea and hyperplasia of skin lymphatics without accompanying changes in blood vasculature. sVegfr-2 inhibited lymphangiogenesis but not hemangiogenesis induced by corneal suture injury or transplantation, enhanced corneal allograft survival, and suppressed lymphangioma cellular proliferation. Naturally occurring sVegfr-2 is a molecular uncoupler of blood and lymphatic vessels whose modulation might have a therapeutic role in lymphatic vascular malformations, transplantation, and potentially in tumor lymphangiogenesis and lymphedema.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Ferrara, N" uniqKey="Ferrara N">N Ferrara</name></author><author><name sortKey="Kerbel, Rs" uniqKey="Kerbel R">RS Kerbel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carmeliet, P" uniqKey="Carmeliet P">P Carmeliet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fenwick, A" uniqKey="Fenwick A">A Fenwick</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carmeliet, P" uniqKey="Carmeliet P">P Carmeliet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ferrara, N" uniqKey="Ferrara N">N 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Crowley</name></author><author><name sortKey="Cunningham, B" uniqKey="Cunningham B">B Cunningham</name></author><author><name sortKey="Wells, Ja" uniqKey="Wells J">JA Wells</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wiesmann, C" uniqKey="Wiesmann C">C Wiesmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goldman, J" uniqKey="Goldman J">J Goldman</name></author><author><name sortKey="Le, Tx" uniqKey="Le T">TX Le</name></author><author><name sortKey="Skobe, M" uniqKey="Skobe M">M Skobe</name></author><author><name sortKey="Swartz, Ma" uniqKey="Swartz M">MA Swartz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vasioukhin, V" uniqKey="Vasioukhin V">V Vasioukhin</name></author><author><name sortKey="Degenstein, L" uniqKey="Degenstein L">L Degenstein</name></author><author><name sortKey="Wise, B" uniqKey="Wise B">B Wise</name></author><author><name sortKey="Fuchs, E" 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sortKey="Ho, Cc" uniqKey="Ho C">CC Ho</name></author><author><name sortKey="Huang, Ph" uniqKey="Huang P">PH Huang</name></author><author><name sortKey="Hsu, Sm" uniqKey="Hsu S">SM Hsu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Norgall, S" uniqKey="Norgall S">S Norgall</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wilting, J" uniqKey="Wilting J">J Wilting</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Azar, Dt" uniqKey="Azar D">DT Azar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kerjaschki, D" uniqKey="Kerjaschki D">D Kerjaschki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brideau, G" uniqKey="Brideau G">G Brideau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kojima, T" uniqKey="Kojima T">T Kojima</name></author><author><name sortKey="Azar, Dt" uniqKey="Azar D">DT Azar</name></author><author><name sortKey="Chang, Jh" uniqKey="Chang J">JH Chang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bielenberg, Dr" uniqKey="Bielenberg D">DR Bielenberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oka, M" uniqKey="Oka M">M Oka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Skobe, M" uniqKey="Skobe M">M Skobe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mandriota, Sj" uniqKey="Mandriota S">SJ Mandriota</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brakenhielm, E" uniqKey="Brakenhielm E">E Brakenhielm</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="He, Y" uniqKey="He Y">Y He</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hirakawa, S" uniqKey="Hirakawa S">S Hirakawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ando, T" uniqKey="Ando T">T Ando</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Allemagne</li><li>Japon</li><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Albuquerque, Romulo J C" sort="Albuquerque, Romulo J C" uniqKey="Albuquerque R" first="Romulo J. C." last="Albuquerque">Romulo J. C. Albuquerque</name></noRegion><name sortKey="Albuquerque, Romulo J C" sort="Albuquerque, Romulo J C" uniqKey="Albuquerque R" first="Romulo J. C." last="Albuquerque">Romulo J. C. Albuquerque</name><name sortKey="Alexander, Jonathan S" sort="Alexander, Jonathan S" uniqKey="Alexander J" first="Jonathan S." last="Alexander">Jonathan S. Alexander</name><name sortKey="Ambati, Balamurali K" sort="Ambati, Balamurali K" uniqKey="Ambati B" first="Balamurali K." last="Ambati">Balamurali K. Ambati</name><name sortKey="Ambati, Balamurali K" sort="Ambati, Balamurali K" uniqKey="Ambati B" first="Balamurali K." last="Ambati">Balamurali K. Ambati</name><name sortKey="Ambati, Jayakrishna" sort="Ambati, Jayakrishna" uniqKey="Ambati J" first="Jayakrishna" last="Ambati">Jayakrishna Ambati</name><name sortKey="Ambati, Jayakrishna" sort="Ambati, Jayakrishna" uniqKey="Ambati J" first="Jayakrishna" last="Ambati">Jayakrishna Ambati</name><name sortKey="Baffi, Judit Z" sort="Baffi, Judit Z" uniqKey="Baffi J" first="Judit Z." last="Baffi">Judit Z. Baffi</name><name sortKey="Brekken, Rolf A" sort="Brekken, Rolf A" uniqKey="Brekken R" first="Rolf A." last="Brekken">Rolf A. Brekken</name><name sortKey="Capoor, Seema" sort="Capoor, Seema" uniqKey="Capoor S" first="Seema" last="Capoor">Seema Capoor</name><name sortKey="Chappell, Joe" sort="Chappell, Joe" uniqKey="Chappell J" first="Joe" last="Chappell">Joe Chappell</name><name sortKey="Cho, Won Gil" sort="Cho, Won Gil" uniqKey="Cho W" first="Won Gil" last="Cho">Won Gil Cho</name><name sortKey="Dridi, Sami" sort="Dridi, Sami" uniqKey="Dridi S" first="Sami" last="Dridi">Sami Dridi</name><name sortKey="Green, Martha G" sort="Green, Martha G" uniqKey="Green M" first="Martha G." last="Green">Martha G. Green</name><name sortKey="Kaneko, Hiroki" sort="Kaneko, Hiroki" uniqKey="Kaneko H" first="Hiroki" last="Kaneko">Hiroki Kaneko</name><name sortKey="Kleinman, Mark E" sort="Kleinman, Mark E" uniqKey="Kleinman M" first="Mark E." last="Kleinman">Mark E. Kleinman</name><name sortKey="Peterson, Martha L" sort="Peterson, Martha L" uniqKey="Peterson M" first="Martha L." last="Peterson">Martha L. Peterson</name><name sortKey="Takeda, Atsunobu" sort="Takeda, Atsunobu" uniqKey="Takeda A" first="Atsunobu" last="Takeda">Atsunobu Takeda</name><name sortKey="Yamada, Kiyoshi" sort="Yamada, Kiyoshi" uniqKey="Yamada K" first="Kiyoshi" last="Yamada">Kiyoshi Yamada</name></country><country name="Japon"><noRegion><name sortKey="Hayashi, Takahiko" sort="Hayashi, Takahiko" uniqKey="Hayashi T" first="Takahiko" last="Hayashi">Takahiko Hayashi</name></noRegion><name sortKey="Amano, Shiro" sort="Amano, Shiro" uniqKey="Amano S" first="Shiro" last="Amano">Shiro Amano</name><name sortKey="Hirashima, Masanori" sort="Hirashima, Masanori" uniqKey="Hirashima M" first="Masanori" last="Hirashima">Masanori Hirashima</name><name sortKey="Mizuki, Nobuhisa" sort="Mizuki, Nobuhisa" uniqKey="Mizuki N" first="Nobuhisa" last="Mizuki">Nobuhisa Mizuki</name><name sortKey="Usui, Tomohiko" sort="Usui, Tomohiko" uniqKey="Usui T" first="Tomohiko" last="Usui">Tomohiko Usui</name><name sortKey="Yamagami, Satoru" sort="Yamagami, Satoru" uniqKey="Yamagami S" first="Satoru" last="Yamagami">Satoru Yamagami</name></country><country name="Allemagne"><noRegion><name sortKey="Wilting, Jorg" sort="Wilting, Jorg" uniqKey="Wilting J" first="Jörg" last="Wilting">Jörg Wilting</name></noRegion><name sortKey="Weich, Herbert A" sort="Weich, Herbert A" uniqKey="Weich H" first="Herbert A." last="Weich">Herbert A. 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