Signalling via vascular endothelial growth factor receptor‐3 is sufficient for lymphangiogenesis in transgenic mice
Identifieur interne : 009D22 ( Main/Exploration ); précédent : 009D21; suivant : 009D23Signalling via vascular endothelial growth factor receptor‐3 is sufficient for lymphangiogenesis in transgenic mice
Auteurs : Tanja Veikkola [Finlande, Australie] ; Lotta Jussila [Finlande, Australie] ; Taija Makinen [Finlande] ; Terhi Karpanen [Finlande] ; Michael Jeltsch [Finlande] ; Tatiana V. Petrova [Finlande] ; Hajime Kubo [Finlande] ; Gavin Thurston [États-Unis] ; Donald M. Mcdonald [États-Unis] ; Marc G. Achen [Australie] ; Steven A. Stacker [Australie] ; Kari Alitalo [Finlande]Source :
- The EMBO Journal [ 0261-4189 ] ; 2001-03-15.
Abstract
Vascular endothelial growth factor receptor‐3 (VEGFR‐3) has an essential role in the development of embryonic blood vessels; however, after midgestation its expression becomes restricted mainly to the developing lymphatic vessels. The VEGFR‐3 ligand VEGF‐C stimulates lymphangiogenesis in transgenic mice and in chick chorioallantoic membrane. As VEGF‐C also binds VEGFR‐2, which is expressed in lymphatic endothelia, it is not clear which receptors are responsible for the lymphangiogenic effects of VEGF‐C. VEGF‐D, which binds to the same receptors, has been reported to induce angiogenesis, but its lymphangiogenic potential is not known. In order to define the lymphangiogenic signalling pathway we have created transgenic mice overexpressing a VEGFR‐3‐specific mutant of VEGF‐C (VEGF‐C156S) or VEGF‐D in epidermal keratinocytes under the keratin 14 promoter. Both transgenes induced the growth of lymphatic vessels in the skin, whereas the blood vessel architecture was not affected. Evidence was also obtained that these growth factors act in a paracrine manner in vivo. These results demonstrate that stimulation of the VEGFR‐3 signal transduction pathway is sufficient to induce specifically lymphangiogenesis in vivo.
Url:
- https://api.istex.fr/document/A5E4B731D387BFD771E4E53147B3B22EBAE77849/fulltext/pdf
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC145532
DOI: 10.1093/emboj/20.6.1223
Affiliations:
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xml:lang="fr">Australie</country><wicri:regionArea>Ludwig Institute for Cancer Research, PO Box 2008, Royal Melbourne Hospital, Parkville, Victoria, 3050</wicri:regionArea><wicri:noRegion>3050</wicri:noRegion></affiliation></author><author><name sortKey="Jussila, Lotta" sort="Jussila, Lotta" uniqKey="Jussila L" first="Lotta" last="Jussila">Lotta Jussila</name><affiliation wicri:level="4"><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute, University of Helsinki, PO Box 21 (Haartmaninkatu 3), 00014, Helsinki</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Australie</country><wicri:regionArea>Ludwig Institute for Cancer Research, PO Box 2008, Royal Melbourne Hospital, Parkville, 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Haartman Institute, University of Helsinki, PO Box 21 (Haartmaninkatu 3), 00014, Helsinki</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Jeltsch, Michael" sort="Jeltsch, Michael" uniqKey="Jeltsch M" first="Michael" last="Jeltsch">Michael Jeltsch</name><affiliation wicri:level="4"><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute, University of Helsinki, PO Box 21 (Haartmaninkatu 3), 00014, Helsinki</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Petrova, Tatiana V" sort="Petrova, Tatiana V" uniqKey="Petrova T" first="Tatiana V." last="Petrova">Tatiana V. Petrova</name><affiliation wicri:level="4"><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute, University of Helsinki, PO Box 21 (Haartmaninkatu 3), 00014, Helsinki</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Kubo, Hajime" sort="Kubo, Hajime" uniqKey="Kubo H" first="Hajime" last="Kubo">Hajime Kubo</name><affiliation wicri:level="4"><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute, University of Helsinki, PO Box 21 (Haartmaninkatu 3), 00014, Helsinki</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Thurston, Gavin" sort="Thurston, Gavin" uniqKey="Thurston G" first="Gavin" last="Thurston">Gavin Thurston</name><affiliation wicri:level="3"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Anatomy and Cardiovascular Research Institute, University of California, CA, 94143, San Francisco</wicri:regionArea><placeName><settlement type="city">San Francisco</settlement><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Mcdonald, Donald M" sort="Mcdonald, Donald M" uniqKey="Mcdonald D" first="Donald M." last="Mcdonald">Donald M. Mcdonald</name><affiliation wicri:level="3"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Anatomy and Cardiovascular Research Institute, University of California, CA, 94143, San Francisco</wicri:regionArea><placeName><settlement type="city">San Francisco</settlement><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Achen, Marc G" sort="Achen, Marc G" uniqKey="Achen M" first="Marc G." last="Achen">Marc G. Achen</name><affiliation wicri:level="1"><country xml:lang="fr">Australie</country><wicri:regionArea>Ludwig Institute for Cancer Research, PO Box 2008, Royal Melbourne Hospital, Parkville, Victoria, 3050</wicri:regionArea><wicri:noRegion>3050</wicri:noRegion></affiliation></author><author><name sortKey="Stacker, Steven A" sort="Stacker, Steven A" uniqKey="Stacker S" first="Steven A." last="Stacker">Steven A. Stacker</name><affiliation wicri:level="1"><country xml:lang="fr">Australie</country><wicri:regionArea>Ludwig Institute for Cancer Research, PO Box 2008, Royal Melbourne Hospital, Parkville, Victoria, 3050</wicri:regionArea><wicri:noRegion>3050</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="4"><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute, University of Helsinki, PO Box 21 (Haartmaninkatu 3), 00014, Helsinki</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><orgName type="university">Université d'Helsinki</orgName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Finlande</country><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><orgName type="university">Université d'Helsinki</orgName></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">The EMBO Journal</title><title level="j" type="alt">THE EMBO JOURNAL</title><idno type="ISSN">0261-4189</idno><idno type="eISSN">1460-2075</idno><imprint><biblScope unit="vol">20</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="1223">1223</biblScope><biblScope unit="page" to="1231">1231</biblScope><biblScope unit="page-count">9</biblScope><publisher>John Wiley & Sons, Ltd</publisher><pubPlace>Chichester, UK</pubPlace><date type="published" when="2001-03-15">2001-03-15</date></imprint><idno type="ISSN">0261-4189</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0261-4189</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Vascular endothelial growth factor receptor‐3 (VEGFR‐3) has an essential role in the development of embryonic blood vessels; however, after midgestation its expression becomes restricted mainly to the developing lymphatic vessels. The VEGFR‐3 ligand VEGF‐C stimulates lymphangiogenesis in transgenic mice and in chick chorioallantoic membrane. As VEGF‐C also binds VEGFR‐2, which is expressed in lymphatic endothelia, it is not clear which receptors are responsible for the lymphangiogenic effects of VEGF‐C. VEGF‐D, which binds to the same receptors, has been reported to induce angiogenesis, but its lymphangiogenic potential is not known. In order to define the lymphangiogenic signalling pathway we have created transgenic mice overexpressing a VEGFR‐3‐specific mutant of VEGF‐C (VEGF‐C156S) or VEGF‐D in epidermal keratinocytes under the keratin 14 promoter. Both transgenes induced the growth of lymphatic vessels in the skin, whereas the blood vessel architecture was not affected. Evidence was also obtained that these growth factors act in a paracrine manner in vivo. These results demonstrate that stimulation of the VEGFR‐3 signal transduction pathway is sufficient to induce specifically lymphangiogenesis in vivo.</div></front></TEI><affiliations><list><country><li>Australie</li><li>Finlande</li><li>États-Unis</li></country><region><li>Californie</li><li>Uusimaa</li></region><settlement><li>Helsinki</li><li>San Francisco</li></settlement><orgName><li>Université d'Helsinki</li></orgName></list><tree><country name="Finlande"><region name="Uusimaa"><name sortKey="Veikkola, Tanja" sort="Veikkola, Tanja" uniqKey="Veikkola T" first="Tanja" last="Veikkola">Tanja Veikkola</name></region><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><name sortKey="Jeltsch, Michael" sort="Jeltsch, Michael" uniqKey="Jeltsch M" first="Michael" last="Jeltsch">Michael Jeltsch</name><name sortKey="Jussila, Lotta" sort="Jussila, Lotta" uniqKey="Jussila L" first="Lotta" last="Jussila">Lotta Jussila</name><name sortKey="Karpanen, Terhi" sort="Karpanen, Terhi" uniqKey="Karpanen T" first="Terhi" last="Karpanen">Terhi Karpanen</name><name sortKey="Kubo, Hajime" sort="Kubo, Hajime" uniqKey="Kubo H" first="Hajime" last="Kubo">Hajime Kubo</name><name sortKey="Makinen, Taija" sort="Makinen, Taija" uniqKey="Makinen T" first="Taija" last="Makinen">Taija Makinen</name><name sortKey="Petrova, Tatiana V" sort="Petrova, Tatiana V" uniqKey="Petrova T" first="Tatiana V." last="Petrova">Tatiana V. Petrova</name></country><country name="Australie"><noRegion><name sortKey="Veikkola, Tanja" sort="Veikkola, Tanja" uniqKey="Veikkola T" first="Tanja" last="Veikkola">Tanja Veikkola</name></noRegion><name sortKey="Achen, Marc G" sort="Achen, Marc G" uniqKey="Achen M" first="Marc G." last="Achen">Marc G. Achen</name><name sortKey="Jussila, Lotta" sort="Jussila, Lotta" uniqKey="Jussila L" first="Lotta" last="Jussila">Lotta Jussila</name><name sortKey="Stacker, Steven A" sort="Stacker, Steven A" uniqKey="Stacker S" first="Steven A." last="Stacker">Steven A. Stacker</name></country><country name="États-Unis"><region name="Californie"><name sortKey="Thurston, Gavin" sort="Thurston, Gavin" uniqKey="Thurston G" first="Gavin" last="Thurston">Gavin Thurston</name></region><name sortKey="Mcdonald, Donald M" sort="Mcdonald, Donald M" uniqKey="Mcdonald D" first="Donald M." last="Mcdonald">Donald M. Mcdonald</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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