{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T23:06:09Z","timestamp":1767135969924,"version":"build-2238731810"},"reference-count":57,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T00:00:00Z","timestamp":1607299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007065","name":"Universit\u00e0 degli Studi di Salerno","doi-asserted-by":"publisher","award":["FARB 2018"],"award-info":[{"award-number":["FARB 2018"]}],"id":[{"id":"10.13039\/501100007065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007065","name":"Universit\u00e0 degli Studi di Salerno","doi-asserted-by":"publisher","award":["2019"],"award-info":[{"award-number":["2019"]}],"id":[{"id":"10.13039\/501100007065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mesoglycan is a drug based on a mixture of glycosaminoglycans mainly used for the treatment of blood vessel diseases acting as antithrombotic and profibrinolytic drugs. Besides the numerous clinical studies, there is\u00a0no information about its function on the fibrinolytic cascade. Here, we have elucidated the mechanism of action by which mesoglycan induces the activation of plasmin from endothelial cells. Surprisingly, by a proteomic analysis, we found that, following mesoglycan treatment, these cells show a notable amount of annexin A2 (ANXA2) at the plasma membrane. This protein has been widely associated with fibrinolysis and appears able to move to the membrane when phosphorylated. In our model, this translocation has proven to enhance cell migration, invasion, and angiogenesis. Furthermore, the interaction of mesoglycan with syndecan 4 (SDC4), a coreceptor belonging to the class of heparan sulfate proteoglycans, represents the upstream event of the ANXA2 behavior. Indeed, the activation of SDC4 triggers the motility of endothelial cells culminating in angiogenesis. Interestingly, mesoglycan can induce the release of plasmin in endothelial cell supernatants only in the presence of ANXA2. This evaluation suggests that mesoglycan triggers the formation of a chain mechanism starting from the activation of SDC4, and the related cascade of events, including src complex and PKC\u03b1 activation, promoting the phosphorylation of ANXA2 and its translocation to plasma membrane. This indicates a connection among mesoglycan, SDC4\u2010(PKC\u03b1\u2010src), and ANXA2 which, in turn, links the tissue plasminogen activator bringing it closer to plasminogen. This latter is so cleaved to release the plasmin and degrade fibrin sleeves.<\/jats:p>","DOI":"10.1002\/jcp.30207","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T09:10:39Z","timestamp":1607332239000},"page":"4926-4943","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["RETRACTED: Mesoglycan exerts its fibrinolytic effect through the activation of annexin A2"],"prefix":"10.1002","volume":"236","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5036-7869","authenticated-orcid":false,"given":"Raffaella","family":"Belvedere","sequence":"first","affiliation":[{"name":"Department of Pharmacy University of Salerno  Fisciano (SA) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7244-0297","authenticated-orcid":false,"given":"Elva","family":"Morretta","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Salerno  Fisciano (SA) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1040-7288","authenticated-orcid":false,"given":"Emanuela","family":"Pessolano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Salerno  Fisciano (SA) Italy"},{"name":"The William Harvey Research Institute,\u00a0Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nunzia","family":"Novizio","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Salerno  Fisciano (SA) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Tosco","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Salerno  Fisciano (SA) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amalia","family":"Porta","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Salerno  Fisciano (SA) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Whiteford","sequence":"additional","affiliation":[{"name":"The William Harvey Research Institute,\u00a0Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro","family":"Perretti","sequence":"additional","affiliation":[{"name":"The William Harvey Research Institute,\u00a0Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amelia","family":"Filippelli","sequence":"additional","affiliation":[{"name":"Department of Medicine,\u00a0Surgery, and Dentistry University of Salerno  Baronissi (SA) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1337-2909","authenticated-orcid":false,"given":"Maria Chiara","family":"Monti","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Salerno  Fisciano (SA) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6945-5295","authenticated-orcid":false,"given":"Antonello","family":"Petrella","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Salerno  Fisciano (SA) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,12,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2006-0559"},{"key":"e_1_2_10_3_1","first-page":"741","article-title":"Effectiveness of mesoglycan in patients with previous deep venous thrombosis and chronic venous insufficiency","volume":"55","author":"Andreozzi G. 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