Local inhibition of elastase reduces EMILIN1 cleavage reactivating lymphatic vessel function in a mouse lymphoedema model
Identifieur interne : 000E98 ( Main/Exploration ); précédent : 000E97; suivant : 000E99Local inhibition of elastase reduces EMILIN1 cleavage reactivating lymphatic vessel function in a mouse lymphoedema model
Auteurs : Eliana Pivetta [Italie] ; Bruna Wassermann [Italie] ; Lisa Del Bel Belluz [Italie, Suède] ; Carla Danussi [Italie, États-Unis] ; Teresa Maria Elisa Modica [Italie] ; Orlando Maiorani [Italie] ; Giulia Bosisio [Italie] ; Francesco Boccardo [Italie] ; Vincenzo Canzonieri [Italie] ; Alfonso Colombatti [Italie] ; Paola Spessotto [Italie]Source :
- Clinical Science (London, England : 1979) [ 0143-5221 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Cellules cultivées, Cellules endothéliales (physiologie), Femelle, Glycoprotéines membranaires (physiologie), Humains, Infiltration par les neutrophiles, Lymphoedème (métabolisme), Lymphoedème (traitement médicamenteux), Modèles animaux de maladie humaine, Protéines sécrétoires inhibitrices de protéinases (pharmacologie), Protéines sécrétoires inhibitrices de protéinases (usage thérapeutique), Souris, Souris de lignée C57BL, Vaisseaux lymphatiques (), Vaisseaux lymphatiques (physiologie).
- MESH :
- métabolisme : Lymphoedème.
- pharmacologie : Protéines sécrétoires inhibitrices de protéinases.
- physiologie : Cellules endothéliales, Glycoprotéines membranaires, Vaisseaux lymphatiques.
- traitement médicamenteux : Lymphoedème.
- usage thérapeutique : Protéines sécrétoires inhibitrices de protéinases.
- Animaux, Cellules cultivées, Femelle, Humains, Infiltration par les neutrophiles, Modèles animaux de maladie humaine, Souris, Souris de lignée C57BL, Vaisseaux lymphatiques.
English descriptors
- KwdEn :
- Animals, Cells, Cultured, Disease Models, Animal, Endothelial Cells (physiology), Female, Humans, Lymphatic Vessels (drug effects), Lymphatic Vessels (physiology), Lymphedema (drug therapy), Lymphedema (metabolism), Membrane Glycoproteins (physiology), Mice, Mice, Inbred C57BL, Neutrophil Infiltration, Proteinase Inhibitory Proteins, Secretory (pharmacology), Proteinase Inhibitory Proteins, Secretory (therapeutic use).
- MESH :
- chemical , pharmacology : Proteinase Inhibitory Proteins, Secretory.
- chemical , physiology : Membrane Glycoproteins.
- drug effects : Lymphatic Vessels.
- drug therapy : Lymphedema.
- metabolism : Lymphedema.
- physiology : Endothelial Cells, Lymphatic Vessels.
- chemical , therapeutic use : Proteinase Inhibitory Proteins, Secretory.
- Animals, Cells, Cultured, Disease Models, Animal, Female, Humans, Mice, Mice, Inbred C57BL, Neutrophil Infiltration.
Abstract
Lymphatic vasculature critically depends on the connections of lymphatic endothelial cells with the extracellular matrix (ECM), which are mediated by anchoring filaments (AFs). The ECM protein EMILIN1 is a component of AFs and is involved in the regulation of lymphatic vessel functions: accordingly,
Url:
DOI: 10.1042/CS20160064
PubMed: 26920215
PubMed Central: 4888021
Affiliations:
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National Cancer Institute, 33081, Aviano, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano</wicri:regionArea><wicri:noRegion>Aviano</wicri:noRegion></affiliation></author><author><name sortKey="Wassermann, Bruna" sort="Wassermann, Bruna" uniqKey="Wassermann B" first="Bruna" last="Wassermann">Bruna Wassermann</name><affiliation wicri:level="1"><nlm:aff id="A1">Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano</wicri:regionArea><wicri:noRegion>Aviano</wicri:noRegion></affiliation></author><author><name sortKey="Belluz, Lisa Del Bel" sort="Belluz, Lisa Del Bel" uniqKey="Belluz L" first="Lisa Del Bel" last="Belluz">Lisa Del Bel Belluz</name><affiliation wicri:level="1"><nlm:aff id="A1">Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano</wicri:regionArea><wicri:noRegion>Aviano</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm</wicri:regionArea><wicri:noRegion>SE-171 77 Stockholm</wicri:noRegion></affiliation></author><author><name sortKey="Danussi, Carla" sort="Danussi, Carla" uniqKey="Danussi C" first="Carla" last="Danussi">Carla Danussi</name><affiliation wicri:level="1"><nlm:aff id="A1">Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano</wicri:regionArea><wicri:noRegion>Aviano</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, U.S.A.</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065</wicri:regionArea><wicri:noRegion>NY 10065</wicri:noRegion></affiliation></author><author><name sortKey="Modica, Teresa Maria Elisa" sort="Modica, Teresa Maria Elisa" uniqKey="Modica T" first="Teresa Maria Elisa" last="Modica">Teresa Maria Elisa Modica</name><affiliation wicri:level="1"><nlm:aff id="A1">Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano</wicri:regionArea><wicri:noRegion>Aviano</wicri:noRegion></affiliation></author><author><name sortKey="Maiorani, Orlando" sort="Maiorani, Orlando" uniqKey="Maiorani O" first="Orlando" last="Maiorani">Orlando Maiorani</name><affiliation wicri:level="1"><nlm:aff id="A1">Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano</wicri:regionArea><wicri:noRegion>Aviano</wicri:noRegion></affiliation></author><author><name sortKey="Bosisio, Giulia" sort="Bosisio, Giulia" uniqKey="Bosisio G" first="Giulia" last="Bosisio">Giulia Bosisio</name><affiliation wicri:level="1"><nlm:aff id="A1">Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano</wicri:regionArea><wicri:noRegion>Aviano</wicri:noRegion></affiliation></author><author><name sortKey="Boccardo, Francesco" sort="Boccardo, Francesco" uniqKey="Boccardo F" first="Francesco" last="Boccardo">Francesco Boccardo</name><affiliation wicri:level="1"><nlm:aff id="A4">Department of Surgery–Unit of Lymphatic Surgery, IRCCS S. Martino University Hospital–IST, National Institute for Cancer Research, University of Genoa, 16132 Genoa, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Surgery–Unit of Lymphatic Surgery, IRCCS S. Martino University Hospital–IST, National Institute for Cancer Research, University of Genoa, 16132 Genoa</wicri:regionArea><wicri:noRegion>16132 Genoa</wicri:noRegion></affiliation></author><author><name sortKey="Canzonieri, Vincenzo" sort="Canzonieri, Vincenzo" uniqKey="Canzonieri V" first="Vincenzo" last="Canzonieri">Vincenzo Canzonieri</name><affiliation wicri:level="1"><nlm:aff id="A5">Division of Pathology, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Division of Pathology, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano</wicri:regionArea><wicri:noRegion>Aviano</wicri:noRegion></affiliation></author><author><name sortKey="Colombatti, Alfonso" sort="Colombatti, Alfonso" uniqKey="Colombatti A" first="Alfonso" last="Colombatti">Alfonso Colombatti</name><affiliation wicri:level="1"><nlm:aff id="A1">Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano</wicri:regionArea><wicri:noRegion>Aviano</wicri:noRegion></affiliation></author><author><name sortKey="Spessotto, Paola" sort="Spessotto, Paola" uniqKey="Spessotto P" first="Paola" last="Spessotto">Paola Spessotto</name><affiliation wicri:level="1"><nlm:aff id="A1">Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano</wicri:regionArea><wicri:noRegion>Aviano</wicri:noRegion></affiliation></author></analytic><series><title level="j">Clinical Science (London, England : 1979)</title><idno type="ISSN">0143-5221</idno><idno type="eISSN">1470-8736</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Cells, Cultured</term><term>Disease Models, Animal</term><term>Endothelial Cells (physiology)</term><term>Female</term><term>Humans</term><term>Lymphatic Vessels (drug effects)</term><term>Lymphatic Vessels (physiology)</term><term>Lymphedema (drug therapy)</term><term>Lymphedema (metabolism)</term><term>Membrane Glycoproteins (physiology)</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Neutrophil Infiltration</term><term>Proteinase Inhibitory Proteins, Secretory (pharmacology)</term><term>Proteinase Inhibitory Proteins, Secretory (therapeutic use)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Cellules cultivées</term><term>Cellules endothéliales (physiologie)</term><term>Femelle</term><term>Glycoprotéines membranaires (physiologie)</term><term>Humains</term><term>Infiltration par les neutrophiles</term><term>Lymphoedème (métabolisme)</term><term>Lymphoedème (traitement médicamenteux)</term><term>Modèles animaux de maladie humaine</term><term>Protéines sécrétoires inhibitrices de protéinases (pharmacologie)</term><term>Protéines sécrétoires inhibitrices de protéinases (usage thérapeutique)</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Vaisseaux lymphatiques ()</term><term>Vaisseaux lymphatiques (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Proteinase Inhibitory Proteins, Secretory</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Membrane Glycoproteins</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Lymphatic Vessels</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Lymphedema</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lymphedema</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Lymphoedème</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Protéines sécrétoires inhibitrices de protéinases</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Cellules endothéliales</term><term>Glycoprotéines membranaires</term><term>Vaisseaux lymphatiques</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Endothelial Cells</term><term>Lymphatic Vessels</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Proteinase Inhibitory Proteins, Secretory</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Lymphoedème</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Protéines sécrétoires inhibitrices de protéinases</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cells, Cultured</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Neutrophil Infiltration</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules cultivées</term><term>Femelle</term><term>Humains</term><term>Infiltration par les neutrophiles</term><term>Modèles animaux de maladie humaine</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Vaisseaux lymphatiques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Lymphatic vasculature critically depends on the connections of lymphatic endothelial cells with the extracellular matrix (ECM), which are mediated by anchoring filaments (AFs). The ECM protein EMILIN1 is a component of AFs and is involved in the regulation of lymphatic vessel functions: accordingly, <italic>Emilin1<sup>−/−</sup></italic> mice display lymphatic vascular morphological alterations, leading to functional defects such as mild lymphoedema, lymph leakage and compromised lymph drainage. In the present study, using a mouse post-surgical tail lymphoedema model, we show that the acute phase of acquired lymphoedema correlates with EMILIN1 degradation due to neutrophil elastase (NE) released by infiltrating neutrophils. As a consequence, the intercellular junctions of lymphatic endothelial cells are weakened and drainage to regional lymph nodes is severely affected. The local administration of sivelestat, a specific NE inhibitor, prevents EMILIN1 degradation and reduces lymphoedema, restoring a normal lymphatic functionality. The finding that, in human secondary lymphoedema samples, we also detected cleaved EMILIN1 with the typical bands of an NE-dependent pattern of fragmentation establishes a rationale for a powerful strategy that targets NE inhibition. In conclusion, the attempts to block EMILIN1 degradation locally represent the basis for a novel ‘ECM’ pharmacological approach to assessing new lymphoedema treatments.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Alitalo, K" uniqKey="Alitalo K">K. Alitalo</name></author><author><name sortKey="Tammela, T" uniqKey="Tammela T">T. Tammela</name></author><author><name sortKey="Petrova, T V" uniqKey="Petrova T">T.V. Petrova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gerli, R" uniqKey="Gerli R">R. Gerli</name></author><author><name sortKey="Ibba, L" uniqKey="Ibba L">L. Ibba</name></author><author><name sortKey="Fruschelli, C" uniqKey="Fruschelli C">C. 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Rigby</name></author><author><name sortKey="Ferguson, D J" uniqKey="Ferguson D">D.J. Ferguson</name></author><author><name sortKey="Johnson, L A" uniqKey="Johnson L">L.A. Johnson</name></author><author><name sortKey="Jackson, D G" uniqKey="Jackson D">D.G. Jackson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Avraham, T" uniqKey="Avraham T">T. Avraham</name></author><author><name sortKey="Daluvoy, S" uniqKey="Daluvoy S">S. Daluvoy</name></author><author><name sortKey="Zampell, J" uniqKey="Zampell J">J. Zampell</name></author><author><name sortKey="Yan, A" uniqKey="Yan A">A. Yan</name></author><author><name sortKey="Haviv, Y S" uniqKey="Haviv Y">Y.S. Haviv</name></author><author><name sortKey="Rockson, S G" uniqKey="Rockson S">S.G. Rockson</name></author><author><name sortKey="Mehrara, B J" uniqKey="Mehrara B">B.J. Mehrara</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Italie</li><li>Suède</li><li>États-Unis</li></country></list><tree><country name="Italie"><noRegion><name sortKey="Pivetta, Eliana" sort="Pivetta, Eliana" uniqKey="Pivetta E" first="Eliana" last="Pivetta">Eliana Pivetta</name></noRegion><name sortKey="Belluz, Lisa Del Bel" sort="Belluz, Lisa Del Bel" uniqKey="Belluz L" first="Lisa Del Bel" last="Belluz">Lisa Del Bel Belluz</name><name sortKey="Boccardo, Francesco" sort="Boccardo, Francesco" uniqKey="Boccardo F" first="Francesco" last="Boccardo">Francesco Boccardo</name><name sortKey="Bosisio, Giulia" sort="Bosisio, Giulia" uniqKey="Bosisio G" first="Giulia" last="Bosisio">Giulia Bosisio</name><name sortKey="Canzonieri, Vincenzo" sort="Canzonieri, Vincenzo" uniqKey="Canzonieri V" first="Vincenzo" last="Canzonieri">Vincenzo Canzonieri</name><name sortKey="Colombatti, Alfonso" sort="Colombatti, Alfonso" uniqKey="Colombatti A" first="Alfonso" last="Colombatti">Alfonso Colombatti</name><name sortKey="Danussi, Carla" sort="Danussi, Carla" uniqKey="Danussi C" first="Carla" last="Danussi">Carla Danussi</name><name sortKey="Maiorani, Orlando" sort="Maiorani, Orlando" uniqKey="Maiorani O" first="Orlando" last="Maiorani">Orlando Maiorani</name><name sortKey="Modica, Teresa Maria Elisa" sort="Modica, Teresa Maria Elisa" uniqKey="Modica T" first="Teresa Maria Elisa" last="Modica">Teresa Maria Elisa Modica</name><name sortKey="Spessotto, Paola" sort="Spessotto, Paola" uniqKey="Spessotto P" first="Paola" last="Spessotto">Paola Spessotto</name><name sortKey="Wassermann, Bruna" sort="Wassermann, Bruna" uniqKey="Wassermann B" first="Bruna" last="Wassermann">Bruna Wassermann</name></country><country name="Suède"><noRegion><name sortKey="Belluz, Lisa Del Bel" sort="Belluz, Lisa Del Bel" uniqKey="Belluz L" first="Lisa Del Bel" last="Belluz">Lisa Del Bel Belluz</name></noRegion></country><country name="États-Unis"><noRegion><name sortKey="Danussi, Carla" sort="Danussi, Carla" uniqKey="Danussi C" first="Carla" last="Danussi">Carla Danussi</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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