{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T08:19:29Z","timestamp":1762157969140,"version":"build-2065373602"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Platelet hyperreactivity contributes to the pathogenesis of COVID\u201019, which is associated with a hypercoagulability state and thrombosis disorder. It has been demonstrated that Vitamin D deficiency is associated with the severity of COVID\u201019 infection. Vitamin D supplement is widely used as a dietary supplement due to its safety and health benefits. In this study, we investigated the direct effects and underlying mechanisms of 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> on platelet hyperreactivity induced by SRAS\u2010CoV\u20102 spike protein via Western blot and platelet functional studies in vitro. Firstly, we found that 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> attenuated platelet aggregation and Src\u2010mediated signaling. We further observed that 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> attenuated spike protein\u2010potentiated platelet aggregation in vitro. Mechanistically, 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> attenuated spike protein upregulated\u2010integrin \u03b1IIb\u03b23 outside\u2010in signaling such as platelet spreading and the phosphorylation of \u03b23, c\u2010Src and Syk. Moreover, using PP2, the Src family kinase inhibitor to abolish spike protein\u2010stimulated platelet aggregation and integrin \u03b1IIb\u03b23 outside\u2010in signaling, the combination of PP2 and 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> did not show additive inhibitory effects on spike protein\u2010potentiated platelet aggregation and the phosphorylation of \u03b23, c\u2010Src and Syk. Thus, our data suggest that 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> attenuates platelet aggregation potentiated by spike protein via downregulating integrin \u03b1IIb\u03b23 outside\u2010in signaling.<\/jats:p>","DOI":"10.1002\/cbf.4039","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T02:08:27Z","timestamp":1715825307000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["1,25\u2010Dihydroxyvitamin D3 attenuates platelet aggregation potentiated by SARS\u2010CoV\u20102 spike protein via inhibiting integrin \u03b1IIb\u03b23 outside\u2010in signaling"],"prefix":"10.1002","volume":"42","author":[{"given":"Ruijie","family":"Wang","sequence":"first","affiliation":[{"name":"School of Public Health (Shenzhen) Shenzhen Campus of Sun Yat\u2010sen University Shenzhen Guangdong Province China"},{"name":"Guangdong Engineering Technology Center of Nutrition Transformation Sun 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