{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:00:18Z","timestamp":1792522818417,"version":"4.5.0"},"reference-count":47,"publisher":"Portland Press Ltd.","issue":"14","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":1149,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,7,1]]},"abstract":"<jats: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, Emilin1\u2212\/\u2212 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 \u2018ECM\u2019 pharmacological approach to assessing new lymphoedema treatments.<\/jats:p>","DOI":"10.1042\/cs20160064","type":"journal-article","created":{"date-parts":[[2016,2,27]],"date-time":"2016-02-27T03:39:02Z","timestamp":1456544342000},"page":"1221-1236","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Local inhibition of elastase reduces EMILIN1 cleavage reactivating lymphatic vessel function in a mouse lymphoedema model"],"prefix":"10.1042","volume":"130","author":[{"given":"Eliana","family":"Pivetta","sequence":"first","affiliation":[{"name":"Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna","family":"Wassermann","sequence":"additional","affiliation":[{"name":"Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa Del\u00a0Bel","family":"Belluz","sequence":"additional","affiliation":[{"name":"Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano, Italy"},{"name":"Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Danussi","sequence":"additional","affiliation":[{"name":"Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano, Italy"},{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa Maria\u00a0Elisa","family":"Modica","sequence":"additional","affiliation":[{"name":"Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orlando","family":"Maiorani","sequence":"additional","affiliation":[{"name":"Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Bosisio","sequence":"additional","affiliation":[{"name":"Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, 33081, Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Boccardo","sequence":"additional","affiliation":[{"name":"Department of Surgery\u2013Unit of Lymphatic Surgery, IRCCS S. 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