Serveur d'exploration sur le lymphœdème

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Tumour necrosis factor superfamily member 15 (Tnfsf15) facilitates lymphangiogenesis via up-regulation of Vegfr3 gene expression in lymphatic endothelial cells.

Identifieur interne : 001660 ( Main/Exploration ); précédent : 001659; suivant : 001661

Tumour necrosis factor superfamily member 15 (Tnfsf15) facilitates lymphangiogenesis via up-regulation of Vegfr3 gene expression in lymphatic endothelial cells.

Auteurs : Ting-Ting Qin [République populaire de Chine] ; Guo-Ce Xu [République populaire de Chine] ; Jian-Wei Qi [République populaire de Chine] ; Gui-Li Yang [République populaire de Chine] ; Kun Zhang [République populaire de Chine] ; Hai-Lin Liu [République populaire de Chine] ; Li-Xia Xu [République populaire de Chine] ; Rong Xiang [République populaire de Chine] ; Guozhi Xiao [République populaire de Chine] ; Huiling Cao [République populaire de Chine] ; Yuquan Wei [République populaire de Chine] ; Qiang-Zhe Zhang [République populaire de Chine] ; Lu-Yuan Li [République populaire de Chine]

Source :

RBID : pubmed:26096340

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English descriptors

Abstract

Lymphangiogenesis is essential in embryonic development but is rare in adults. It occurs, however, in many disease conditions including cancers. Vascular endothelial growth factor-C/D (VEGF-C/D) and VEGF receptor-3 (Vegfr3) play a critical role in the regulation of lymphangiogenesis. We investigated how the VEGF-C/Vegfr3 signalling system is regulated by tumour necrosis factor superfamily member 15 (Tnfsf15), an endothelium-derived cytokine. We report here that Tnfsf15, which is known to induce apoptosis in vascular endothelial cells, can promote lymphatic endothelial cell (LEC) growth and migration, stimulate lymphangiogenesis, and facilitate lymphatic circulation. Treatment of mouse LECs with Tnfsf15 results in up-regulation of Vegfr3 expression; this can be inhibited by gene silencing of death domain-containing receptor-3 (DR3; Tnfrsf25), a cell surface receptor for Tnfsf15, with siRNA, or by blocking Tnfsf15-DR3 interaction with a Tnfsf15 neutralizing antibody, 4-3H. Additionally, Tnfsf15/DR3 signalling pathways in LECs include activation of NF-κB. Tnfsf15-overexpressing transgenic mice exhibit a marked enhancement of lymph drainage; this is confirmed by treatment of wild-type mice with intraperitoneal injection of recombinant Tnfsf15. Moreover, systemic treatment of pregnant Tnfsf15 transgenic mice with 4-3H leads to inhibition of embryonic lymphangiogenesis. Our data indicate that Tnfsf15, a cytokine produced largely by endothelial cells, facilitates lymphangiogenesis by up-regulating Vegfr3 gene expression in LECs, contributing to the maintenance of the homeostasis of the circulatory system. This finding also suggests that Tnfsf15 may be of potential value as a therapeutic tool for the treatment of lymphoedema.

DOI: 10.1002/path.4577
PubMed: 26096340


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<name sortKey="Zhang, Kun" sort="Zhang, Kun" uniqKey="Zhang K" first="Kun" last="Zhang">Kun Zhang</name>
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<name sortKey="Liu, Hai Lin" sort="Liu, Hai Lin" uniqKey="Liu H" first="Hai-Lin" last="Liu">Hai-Lin Liu</name>
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<name sortKey="Xu, Li Xia" sort="Xu, Li Xia" uniqKey="Xu L" first="Li-Xia" last="Xu">Li-Xia Xu</name>
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<name sortKey="Xiang, Rong" sort="Xiang, Rong" uniqKey="Xiang R" first="Rong" last="Xiang">Rong Xiang</name>
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<name sortKey="Xiao, Guozhi" sort="Xiao, Guozhi" uniqKey="Xiao G" first="Guozhi" last="Xiao">Guozhi Xiao</name>
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<term>Animals</term>
<term>Cell Movement</term>
<term>Cell Proliferation</term>
<term>Cells, Cultured</term>
<term>Dose-Response Relationship, Drug</term>
<term>Endothelial Cells (drug effects)</term>
<term>Endothelial Cells (metabolism)</term>
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<term>Lymph (metabolism)</term>
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<term>Lymphatic Vessels (cytology)</term>
<term>Lymphatic Vessels (drug effects)</term>
<term>Lymphatic Vessels (metabolism)</term>
<term>Mice, Inbred BALB C</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Transgenic</term>
<term>NF-kappa B (metabolism)</term>
<term>RNA Interference</term>
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<term>Receptors, Tumor Necrosis Factor, Member 25 (metabolism)</term>
<term>Recombinant Proteins (administration & dosage)</term>
<term>Signal Transduction</term>
<term>Time Factors</term>
<term>Transfection</term>
<term>Tumor Necrosis Factor Ligand Superfamily Member 15 (administration & dosage)</term>
<term>Tumor Necrosis Factor Ligand Superfamily Member 15 (genetics)</term>
<term>Tumor Necrosis Factor Ligand Superfamily Member 15 (metabolism)</term>
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<term>Animaux</term>
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<term>Souris transgéniques</term>
<term>Transduction du signal</term>
<term>Transfection</term>
<term>Vaisseaux lymphatiques ()</term>
<term>Vaisseaux lymphatiques (cytologie)</term>
<term>Vaisseaux lymphatiques (métabolisme)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en">
<term>Recombinant Proteins</term>
<term>Tumor Necrosis Factor Ligand Superfamily Member 15</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>Receptors, Tumor Necrosis Factor, Member 25</term>
<term>Tumor Necrosis Factor Ligand Superfamily Member 15</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>NF-kappa B</term>
<term>Receptors, Tumor Necrosis Factor, Member 25</term>
<term>Tumor Necrosis Factor Ligand Superfamily Member 15</term>
<term>Vascular Endothelial Growth Factor C</term>
<term>Vascular Endothelial Growth Factor Receptor-3</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr">
<term>Membre-15 de la superfamille du facteur de nécrose tumorale</term>
<term>Protéines recombinantes</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr">
<term>Vaisseaux lymphatiques</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en">
<term>Lymphatic Vessels</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>Endothelial Cells</term>
<term>Lymphangiogenesis</term>
<term>Lymphatic Vessels</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Membre-15 de la superfamille du facteur de nécrose tumorale</term>
<term>Membre-25 de la superfamille des récepteurs au TNF</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Endothelial Cells</term>
<term>Lymph</term>
<term>Lymphatic Vessels</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Cellules endothéliales</term>
<term>Facteur de croissance endothéliale vasculaire de type C</term>
<term>Facteur de transcription NF-kappa B</term>
<term>Lymphe</term>
<term>Membre-15 de la superfamille du facteur de nécrose tumorale</term>
<term>Membre-25 de la superfamille des récepteurs au TNF</term>
<term>Récepteur-3 au facteur croissance endothéliale vasculaire</term>
<term>Vaisseaux lymphatiques</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Animals</term>
<term>Cell Movement</term>
<term>Cell Proliferation</term>
<term>Cells, Cultured</term>
<term>Dose-Response Relationship, Drug</term>
<term>Injections, Intraperitoneal</term>
<term>Mice, Inbred BALB C</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Transgenic</term>
<term>RNA Interference</term>
<term>Signal Transduction</term>
<term>Time Factors</term>
<term>Transfection</term>
<term>Up-Regulation</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Animaux</term>
<term>Cellules cultivées</term>
<term>Cellules endothéliales</term>
<term>Facteurs temps</term>
<term>Injections péritoneales</term>
<term>Interférence par ARN</term>
<term>Lymphangiogenèse</term>
<term>Mouvement cellulaire</term>
<term>Prolifération cellulaire</term>
<term>Relation dose-effet des médicaments</term>
<term>Régulation positive</term>
<term>Souris de lignée BALB C</term>
<term>Souris de lignée C57BL</term>
<term>Souris transgéniques</term>
<term>Transduction du signal</term>
<term>Transfection</term>
<term>Vaisseaux lymphatiques</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">Lymphangiogenesis is essential in embryonic development but is rare in adults. It occurs, however, in many disease conditions including cancers. Vascular endothelial growth factor-C/D (VEGF-C/D) and VEGF receptor-3 (Vegfr3) play a critical role in the regulation of lymphangiogenesis. We investigated how the VEGF-C/Vegfr3 signalling system is regulated by tumour necrosis factor superfamily member 15 (Tnfsf15), an endothelium-derived cytokine. We report here that Tnfsf15, which is known to induce apoptosis in vascular endothelial cells, can promote lymphatic endothelial cell (LEC) growth and migration, stimulate lymphangiogenesis, and facilitate lymphatic circulation. Treatment of mouse LECs with Tnfsf15 results in up-regulation of Vegfr3 expression; this can be inhibited by gene silencing of death domain-containing receptor-3 (DR3; Tnfrsf25), a cell surface receptor for Tnfsf15, with siRNA, or by blocking Tnfsf15-DR3 interaction with a Tnfsf15 neutralizing antibody, 4-3H. Additionally, Tnfsf15/DR3 signalling pathways in LECs include activation of NF-κB. Tnfsf15-overexpressing transgenic mice exhibit a marked enhancement of lymph drainage; this is confirmed by treatment of wild-type mice with intraperitoneal injection of recombinant Tnfsf15. Moreover, systemic treatment of pregnant Tnfsf15 transgenic mice with 4-3H leads to inhibition of embryonic lymphangiogenesis. Our data indicate that Tnfsf15, a cytokine produced largely by endothelial cells, facilitates lymphangiogenesis by up-regulating Vegfr3 gene expression in LECs, contributing to the maintenance of the homeostasis of the circulatory system. This finding also suggests that Tnfsf15 may be of potential value as a therapeutic tool for the treatment of lymphoedema.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>République populaire de Chine</li>
</country>
<region>
<li>Guangdong</li>
</region>
<settlement>
<li>Shenzhen</li>
<li>Tianjin</li>
</settlement>
</list>
<tree>
<country name="République populaire de Chine">
<noRegion>
<name sortKey="Qin, Ting Ting" sort="Qin, Ting Ting" uniqKey="Qin T" first="Ting-Ting" last="Qin">Ting-Ting Qin</name>
</noRegion>
<name sortKey="Cao, Huiling" sort="Cao, Huiling" uniqKey="Cao H" first="Huiling" last="Cao">Huiling Cao</name>
<name sortKey="Li, Lu Yuan" sort="Li, Lu Yuan" uniqKey="Li L" first="Lu-Yuan" last="Li">Lu-Yuan Li</name>
<name sortKey="Liu, Hai Lin" sort="Liu, Hai Lin" uniqKey="Liu H" first="Hai-Lin" last="Liu">Hai-Lin Liu</name>
<name sortKey="Qi, Jian Wei" sort="Qi, Jian Wei" uniqKey="Qi J" first="Jian-Wei" last="Qi">Jian-Wei Qi</name>
<name sortKey="Wei, Yuquan" sort="Wei, Yuquan" uniqKey="Wei Y" first="Yuquan" last="Wei">Yuquan Wei</name>
<name sortKey="Xiang, Rong" sort="Xiang, Rong" uniqKey="Xiang R" first="Rong" last="Xiang">Rong Xiang</name>
<name sortKey="Xiao, Guozhi" sort="Xiao, Guozhi" uniqKey="Xiao G" first="Guozhi" last="Xiao">Guozhi Xiao</name>
<name sortKey="Xu, Guo Ce" sort="Xu, Guo Ce" uniqKey="Xu G" first="Guo-Ce" last="Xu">Guo-Ce Xu</name>
<name sortKey="Xu, Li Xia" sort="Xu, Li Xia" uniqKey="Xu L" first="Li-Xia" last="Xu">Li-Xia Xu</name>
<name sortKey="Yang, Gui Li" sort="Yang, Gui Li" uniqKey="Yang G" first="Gui-Li" last="Yang">Gui-Li Yang</name>
<name sortKey="Zhang, Kun" sort="Zhang, Kun" uniqKey="Zhang K" first="Kun" last="Zhang">Kun Zhang</name>
<name sortKey="Zhang, Qiang Zhe" sort="Zhang, Qiang Zhe" uniqKey="Zhang Q" first="Qiang-Zhe" last="Zhang">Qiang-Zhe Zhang</name>
</country>
</tree>
</affiliations>
</record>

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