Lymphangiogenic Gene Therapy With Minimal Blood Vascular Side Effects
Identifieur interne : 009425 ( Main/Exploration ); précédent : 009424; suivant : 009426Lymphangiogenic Gene Therapy With Minimal Blood Vascular Side Effects
Auteurs : Anne Saaristo [Finlande] ; Tanja Veikkola [Finlande] ; Tuomas Tammela [Finlande] ; Berndt Enholm [Finlande] ; Marika J. Karkkainen [Finlande] ; Katri Pajusola [Suisse] ; Hansruedi Bueler [Suisse] ; Seppo Yl Herttuala [Finlande] ; Kari Alitalo [Finlande]Source :
- The Journal of Experimental Medicine [ 0022-1007 ] ; 2002.
Descripteurs français
- KwdFr :
- ARN messager (analyse), Adenoviridae (génétique), Animaux, Dependovirus (génétique), Facteur de croissance endothéliale vasculaire de type C, Facteurs de croissance endothéliale (génétique), Lymphoedème (), Néovascularisation physiologique, Récepteur facteur croissance (physiologie), Récepteur-3 au facteur croissance endothéliale vasculaire, Récepteurs à activité tyrosine kinase (physiologie), Souris, Système lymphatique (embryologie), Système lymphatique (physiologie), Thérapie génétique.
- MESH :
- analyse : ARN messager.
- embryologie : Système lymphatique.
- génétique : Adenoviridae, Dependovirus, Facteurs de croissance endothéliale.
- physiologie : Récepteur facteur croissance, Récepteurs à activité tyrosine kinase, Système lymphatique.
- Animaux, Facteur de croissance endothéliale vasculaire de type C, Lymphoedème, Néovascularisation physiologique, Récepteur-3 au facteur croissance endothéliale vasculaire, Souris, Thérapie génétique.
English descriptors
- KwdEn :
- Adenoviridae (genetics), Animals, Dependovirus (genetics), Endothelial Growth Factors (genetics), Genetic Therapy, Lymphatic System (embryology), Lymphatic System (physiology), Lymphedema (therapy), Mice, Neovascularization, Physiologic, RNA, Messenger (analysis), Receptor Protein-Tyrosine Kinases (physiology), Receptors, Growth Factor (physiology), Vascular Endothelial Growth Factor C, Vascular Endothelial Growth Factor Receptor-3.
- MESH :
- chemical , analysis : RNA, Messenger.
- chemical , genetics : Endothelial Growth Factors.
- embryology : Lymphatic System.
- genetics : Adenoviridae, Dependovirus.
- physiology : Lymphatic System, Receptor Protein-Tyrosine Kinases, Receptors, Growth Factor.
- therapy : Lymphedema.
- Animals, Genetic Therapy, Mice, Neovascularization, Physiologic, Vascular Endothelial Growth Factor C, Vascular Endothelial Growth Factor Receptor-3.
Abstract
Recent work from many laboratories has demonstrated that the vascular endothelial growth factor-C/VEGF-D/VEGFR-3 signaling pathway is crucial for lymphangiogenesis, and that mutations of the
Url:
DOI: 10.1084/jem.20020587
PubMed: 12235206
PubMed Central: 2194057
Affiliations:
- Finlande, Suisse
- Canton de Zurich, Uusimaa
- Helsinki, Zurich
- Université d'Helsinki, Université de Zurich
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Le document en format XML
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Karkkainen</name><affiliation wicri:level="1"><nlm:aff id="aff1">Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki, the Haartman Institute and Helsinki University Central Hospital, University of Helsinki, 00014 Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki, the Haartman Institute and Helsinki University Central Hospital, University of Helsinki, 00014 Helsinki</wicri:regionArea><wicri:noRegion>00014 Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Pajusola, Katri" sort="Pajusola, Katri" uniqKey="Pajusola K" first="Katri" last="Pajusola">Katri Pajusola</name><affiliation wicri:level="4"><nlm:aff id="aff2">Institute of Molecular Biology, University of Zurich, 8057 Zurich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Molecular Biology, University of Zurich, 8057 Zurich</wicri:regionArea><orgName type="university">Université de Zurich</orgName><placeName><settlement type="city">Zurich</settlement><region nuts="3" type="region">Canton de Zurich</region></placeName></affiliation></author><author><name sortKey="Bueler, Hansruedi" sort="Bueler, Hansruedi" uniqKey="Bueler H" first="Hansruedi" last="Bueler">Hansruedi Bueler</name><affiliation wicri:level="4"><nlm:aff id="aff2">Institute of Molecular Biology, University of Zurich, 8057 Zurich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Molecular Biology, University of Zurich, 8057 Zurich</wicri:regionArea><orgName type="university">Université de Zurich</orgName><placeName><settlement type="city">Zurich</settlement><region nuts="3" type="region">Canton de Zurich</region></placeName></affiliation></author><author><name sortKey="Yl Herttuala, Seppo" sort="Yl Herttuala, Seppo" uniqKey="Yl Herttuala S" first="Seppo" last="Yl Herttuala">Seppo Yl Herttuala</name><affiliation wicri:level="1"><nlm:aff id="aff3">A.I. Virtanen Institute and Department of Medicine, University of Kuopio, 70211 Kuopio, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>A.I. 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last="Saaristo">Anne Saaristo</name><affiliation wicri:level="1"><nlm:aff id="aff1">Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki, the Haartman Institute and Helsinki University Central Hospital, University of Helsinki, 00014 Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki, the Haartman Institute and Helsinki University Central Hospital, University of Helsinki, 00014 Helsinki</wicri:regionArea><wicri:noRegion>00014 Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Veikkola, Tanja" sort="Veikkola, Tanja" uniqKey="Veikkola T" first="Tanja" last="Veikkola">Tanja Veikkola</name><affiliation wicri:level="1"><nlm:aff id="aff1">Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki, the Haartman Institute and Helsinki University Central Hospital, University of Helsinki, 00014 Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki, the Haartman Institute and Helsinki University Central Hospital, University of Helsinki, 00014 Helsinki</wicri:regionArea><wicri:noRegion>00014 Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Tammela, Tuomas" sort="Tammela, Tuomas" uniqKey="Tammela T" first="Tuomas" last="Tammela">Tuomas Tammela</name><affiliation wicri:level="1"><nlm:aff id="aff1">Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki, the Haartman Institute and Helsinki University Central Hospital, University of Helsinki, 00014 Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki, the Haartman Institute and Helsinki University Central Hospital, University of Helsinki, 00014 Helsinki</wicri:regionArea><wicri:noRegion>00014 Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Enholm, Berndt" sort="Enholm, Berndt" uniqKey="Enholm B" first="Berndt" last="Enholm">Berndt Enholm</name><affiliation wicri:level="1"><nlm:aff id="aff1">Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki, the Haartman Institute and Helsinki University Central Hospital, University of Helsinki, 00014 Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki, the Haartman Institute and Helsinki University Central Hospital, University of Helsinki, 00014 Helsinki</wicri:regionArea><wicri:noRegion>00014 Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Karkkainen, Marika J" sort="Karkkainen, Marika J" uniqKey="Karkkainen M" first="Marika J." last="Karkkainen">Marika J. Karkkainen</name><affiliation wicri:level="1"><nlm:aff id="aff1">Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki, the Haartman Institute and Helsinki University Central Hospital, University of Helsinki, 00014 Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki, the Haartman Institute and Helsinki University Central Hospital, University of Helsinki, 00014 Helsinki</wicri:regionArea><wicri:noRegion>00014 Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Pajusola, Katri" sort="Pajusola, Katri" uniqKey="Pajusola K" first="Katri" last="Pajusola">Katri Pajusola</name><affiliation wicri:level="4"><nlm:aff id="aff2">Institute of Molecular Biology, University of Zurich, 8057 Zurich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Molecular Biology, University of Zurich, 8057 Zurich</wicri:regionArea><orgName type="university">Université de Zurich</orgName><placeName><settlement type="city">Zurich</settlement><region nuts="3" type="region">Canton de Zurich</region></placeName></affiliation></author><author><name sortKey="Bueler, Hansruedi" sort="Bueler, Hansruedi" uniqKey="Bueler H" first="Hansruedi" last="Bueler">Hansruedi Bueler</name><affiliation wicri:level="4"><nlm:aff id="aff2">Institute of Molecular Biology, University of Zurich, 8057 Zurich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Molecular Biology, University of Zurich, 8057 Zurich</wicri:regionArea><orgName type="university">Université de Zurich</orgName><placeName><settlement type="city">Zurich</settlement><region nuts="3" type="region">Canton de Zurich</region></placeName></affiliation></author><author><name sortKey="Yl Herttuala, Seppo" sort="Yl Herttuala, Seppo" uniqKey="Yl Herttuala S" first="Seppo" last="Yl Herttuala">Seppo Yl Herttuala</name><affiliation wicri:level="1"><nlm:aff id="aff3">A.I. Virtanen Institute and Department of Medicine, University of Kuopio, 70211 Kuopio, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>A.I. Virtanen Institute and Department of Medicine, University of Kuopio, 70211 Kuopio</wicri:regionArea><wicri:noRegion>70211 Kuopio</wicri:noRegion></affiliation></author><author><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><affiliation wicri:level="1"><nlm:aff id="aff1">Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki, the Haartman Institute and Helsinki University Central Hospital, University of Helsinki, 00014 Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki, the Haartman Institute and Helsinki University Central Hospital, University of Helsinki, 00014 Helsinki</wicri:regionArea><wicri:noRegion>00014 Helsinki</wicri:noRegion><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">The Journal of Experimental Medicine</title><idno type="ISSN">0022-1007</idno><idno type="eISSN">1540-9538</idno><imprint><date when="2002">2002</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenoviridae (genetics)</term><term>Animals</term><term>Dependovirus (genetics)</term><term>Endothelial Growth Factors (genetics)</term><term>Genetic Therapy</term><term>Lymphatic System (embryology)</term><term>Lymphatic System (physiology)</term><term>Lymphedema (therapy)</term><term>Mice</term><term>Neovascularization, Physiologic</term><term>RNA, Messenger (analysis)</term><term>Receptor Protein-Tyrosine Kinases (physiology)</term><term>Receptors, Growth Factor (physiology)</term><term>Vascular Endothelial Growth Factor C</term><term>Vascular Endothelial Growth Factor Receptor-3</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN messager (analyse)</term><term>Adenoviridae (génétique)</term><term>Animaux</term><term>Dependovirus (génétique)</term><term>Facteur de croissance endothéliale vasculaire de type C</term><term>Facteurs de croissance endothéliale (génétique)</term><term>Lymphoedème ()</term><term>Néovascularisation physiologique</term><term>Récepteur facteur croissance (physiologie)</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire</term><term>Récepteurs à activité tyrosine kinase (physiologie)</term><term>Souris</term><term>Système lymphatique (embryologie)</term><term>Système lymphatique (physiologie)</term><term>Thérapie génétique</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>RNA, Messenger</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Endothelial Growth Factors</term></keywords><keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>ARN messager</term></keywords><keywords scheme="MESH" qualifier="embryologie" xml:lang="fr"><term>Système lymphatique</term></keywords><keywords scheme="MESH" qualifier="embryology" xml:lang="en"><term>Lymphatic System</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Adenoviridae</term><term>Dependovirus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Adenoviridae</term><term>Dependovirus</term><term>Facteurs de croissance endothéliale</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Récepteur facteur croissance</term><term>Récepteurs à activité tyrosine kinase</term><term>Système lymphatique</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Lymphatic System</term><term>Receptor Protein-Tyrosine Kinases</term><term>Receptors, Growth Factor</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Lymphedema</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Genetic Therapy</term><term>Mice</term><term>Neovascularization, Physiologic</term><term>Vascular Endothelial Growth Factor C</term><term>Vascular Endothelial Growth Factor Receptor-3</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Facteur de croissance endothéliale vasculaire de type C</term><term>Lymphoedème</term><term>Néovascularisation physiologique</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire</term><term>Souris</term><term>Thérapie génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Recent work from many laboratories has demonstrated that the vascular endothelial growth factor-C/VEGF-D/VEGFR-3 signaling pathway is crucial for lymphangiogenesis, and that mutations of the <italic>Vegfr3</italic> gene are associated with hereditary lymphedema. Furthermore, VEGF-C gene transfer to the skin of mice with lymphedema induced a regeneration of the cutaneous lymphatic vessel network. However, as is the case with VEGF, high levels of VEGF-C cause blood vessel growth and leakiness, resulting in tissue edema. To avoid these blood vascular side effects of VEGF-C, we constructed a viral vector for a VEGFR-3–specific mutant form of VEGF-C (VEGF-C156S) for lymphedema gene therapy. We demonstrate that VEGF-C156S potently induces lymphangiogenesis in transgenic mouse embryos, and when applied via viral gene transfer, in normal and lymphedema mice. Importantly, adenoviral VEGF-C156S lacked the blood vascular side effects of VEGF and VEGF-C adenoviruses. In particular, in the lymphedema mice functional cutaneous lymphatic vessels of normal caliber and morphology were detected after long-term expression of VEGF-C156S via an adeno associated virus. These results have important implications for the development of gene therapy for human lymphedema.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Finlande</li><li>Suisse</li></country><region><li>Canton de Zurich</li><li>Uusimaa</li></region><settlement><li>Helsinki</li><li>Zurich</li></settlement><orgName><li>Université d'Helsinki</li><li>Université de Zurich</li></orgName></list><tree><country name="Finlande"><noRegion><name sortKey="Saaristo, Anne" sort="Saaristo, Anne" uniqKey="Saaristo A" first="Anne" last="Saaristo">Anne Saaristo</name></noRegion><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><name sortKey="Enholm, Berndt" sort="Enholm, Berndt" uniqKey="Enholm B" first="Berndt" last="Enholm">Berndt Enholm</name><name sortKey="Karkkainen, Marika J" sort="Karkkainen, Marika J" uniqKey="Karkkainen M" first="Marika J." last="Karkkainen">Marika J. Karkkainen</name><name sortKey="Tammela, Tuomas" sort="Tammela, Tuomas" uniqKey="Tammela T" first="Tuomas" last="Tammela">Tuomas Tammela</name><name sortKey="Veikkola, Tanja" sort="Veikkola, Tanja" uniqKey="Veikkola T" first="Tanja" last="Veikkola">Tanja Veikkola</name><name sortKey="Yl Herttuala, Seppo" sort="Yl Herttuala, Seppo" uniqKey="Yl Herttuala S" first="Seppo" last="Yl Herttuala">Seppo Yl Herttuala</name></country><country name="Suisse"><region name="Canton de Zurich"><name sortKey="Pajusola, Katri" sort="Pajusola, Katri" uniqKey="Pajusola K" first="Katri" last="Pajusola">Katri Pajusola</name></region><name sortKey="Bueler, Hansruedi" sort="Bueler, Hansruedi" uniqKey="Bueler H" first="Hansruedi" last="Bueler">Hansruedi Bueler</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a LymphedemaV1
| This area was generated with Dilib version V0.6.31. |  |