{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T14:54:48Z","timestamp":1793199288485,"version":"4.5.0"},"reference-count":28,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T00:00:00Z","timestamp":1623024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Survivin have been shown to play a crucial role in rheumatoid arthritis (RA); however, the regulatory mechanism of survivin in RA has not been fully elucidated. This study aims to investigate the effect of survivin on the proliferation and apoptosis of human RA fibroblast\u2010like synoviocyte (RA\u2010HFLS) cells in RA and its underlying mechanism through the NOTCH pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The RA synovial tissues of 65 RA patients with partial resection of synovium of knee joint by arthroscopy were collected. The expression of survivin in synovial tissue was detected by immunohistochemistry, and the correlation of survivin expression and clinical\u2010pathological parameters of patients was analyzed. In vitro, the proliferation of HFLS and RA\u2010HFLS were detected by MTT; the apoptosis of HFLS and RA\u2010HFLS were detected by flow cytometry; the expression of survivin proteins, key protein factors (Notch1, Jagged1, Hes1) in the Notch pathway, and angiogenesis\u2010related proteins (vascular endothelial growth factor receptor 1 [VEGFR1], Ang1, Ang2) were determined by western blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that survivin was highly expressed in RA synovial tissues and RA\u2010HFLS cells, and was positively correlated with erythrocyte sedimentation rate, cyclic citrullinated peptide, C\u2010reactive protein, Disease Activity Score of 28 joints and other pathological indexes. Knockdown survivin induces RA\u2010HFLS cell apoptosis, suppresses proliferation and the expression of VEGFR1, Ang1, Ang2. In addition, blocking Notch pathway using FLI\u201006 significantly down\u2010regulated survivin expression. When survivin is up\u2010regulated, it promotes RA\u2010HFLS cell proliferation, the expression of VEGFR1, Ang1, Ang2 and suppresses apoptosis by activating the NOTCH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study confirmed that survivin promotes RA\u2010HFLS cell proliferation, the expression of angiogenesis\u2010related proteins and suppresses apoptosis by activating the NOTCH pathway.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1756-185x.14150","type":"journal-article","created":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T13:41:33Z","timestamp":1623073293000},"page":"922-929","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Survivin promotes rheumatoid arthritis fibroblast\u2010like synoviocyte cell proliferation, and the expression of angiogenesis\u2010related proteins by activating the NOTCH 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