{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T15:17:14Z","timestamp":1783091834405,"version":"3.54.6"},"reference-count":40,"publisher":"Georg Thieme Verlag KG","issue":"02","funder":[{"name":"Italian Ministry of Education, University and Research","award":["Dipartimenti di Eccellenza Program (2018\u20132022) -"],"award-info":[{"award-number":["Dipartimenti di Eccellenza Program (2018\u20132022) -"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:p>\n            Background\u2003The C-type lectin receptor CD93 is a single pass type I transmembrane glycoprotein involved in inflammation, immunity, and angiogenesis. This study investigates the role of CD93 in platelet function. CD93 knockout (KO) mice and wild-type (WT) controls were compared in this study.<\/jats:p><jats:p>\n            Methods\u2003Platelet activation and aggregation were investigated by flow cytometry and light transmission aggregometry, respectively. Protein expression and phosphorylation were analyzed by immunoblotting. Subcellular localization of membrane receptors was investigated by wide-field and confocal microscopy.<\/jats:p><jats:p>\n            Results\u2003The lack of CD93 in mice was not associated to any evident bleeding defect and no alterations of platelet activation were observed upon stimulation with thromboxane A2 analogue and convulxin. Conversely, platelet aggregation induced by stimulation of the thrombin receptor PAR4 was significantly reduced in the absence of CD93. This defect was associated with a significant reduction of \u03b1-granule secretion, integrin \u03b1IIb\u03b23 activation, and protein kinase C (PKC) stimulation. Resting WT and CD93-deficient platelets expressed comparable amounts of PAR4. However, upon stimulation with a PAR4 activating peptide, a more pronounced clearance of PAR4 from the platelet surface was observed in CD93-deficient platelets compared with WT controls. Confocal microscopy analysis revealed a massive movement of PAR4 in cytosolic compartments of activated platelets lacking CD93. Accordingly, platelet desensitization following PAR4 stimulation was more pronounced in CD93 KO platelets compared with WT controls.<\/jats:p><jats:p>\n            Conclusion\u2003These results demonstrate that CD93 supports platelet activation triggered by PAR4 stimulation and is required to stabilize the expression of the thrombin receptor on the cell surface.<\/jats:p>","DOI":"10.1055\/a-2166-5841","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T00:24:38Z","timestamp":1693959878000},"page":"122-134","source":"Crossref","is-referenced-by-count":5,"title":["The C-Type Lectin Receptor CD93 Regulates Platelet Activation and Surface Expression of the Protease Activated Receptor 4"],"prefix":"10.1055","volume":"124","author":[{"given":"Silvia Maria Grazia","family":"Trivigno","sequence":"additional","affiliation":[{"name":"University School for Advanced Studies IUSS, Pavia, Italy"},{"name":"Department of Biology and Biotechnology, University of Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Vismara","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology, University of Pavia, Pavia, Italy"},{"name":"Department of Molecular Medicine, University of Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Canobbio","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology, University of Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Rustichelli","sequence":"additional","affiliation":[{"name":"University School for Advanced Studies IUSS, Pavia, Italy"},{"name":"Department of Biology and Biotechnology, University of Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Galvagni","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Orlandini","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Torti","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology, University of Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianni Francesco","family":"Guidetti","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology, University of Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,9,30]]},"reference":[{"issue":"03","key":"ref1","doi-asserted-by":"crossref","first-page":"411","DOI":"10.2174\/138945012799424651","article-title":"CD93: recent advances and 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