{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:40:22Z","timestamp":1791081622735,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,5,25]],"date-time":"2012-05-25T00:00:00Z","timestamp":1337904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Rheumatoid arthritis (RA) is an inflammatory and angiogenic disease. However, the molecular mechanisms that promote angiogenesis in RA have not been clearly identified. Our objective was to study the role of CD147 in angiogenesis and determine whether the strategy in which CD147 is suppressed might be useful in reducing angiogenesis in RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Correlations among expression levels of CD147, vascular endothelial growth factor (VEGF), and hypoxia\u2010inducible factor 1\u03b1 (HIF\u20101\u03b1) were determined by immunohistochemistry staining. RA fibroblast\u2010like synoviocytes (FLS) cells were cultured under various conditions, and the production of VEGF and HIF\u20101\u03b1 was examined by real\u2010time polymerase chain reaction and enzyme\u2010linked immunosorbent assay. The SCID mouse coimplantation model of RA (SCID\u2010HuRAg) was established, mice were treated with CD147 monoclonal antibody, infliximab, or both CD147 and infliximab, and the volume of the grafts and the average vascular density were measured and analyzed. Western blot analyses were performed to examine the potential signaling pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression levels of CD147 showed significantly positive correlations with VEGF and HIF\u20101\u03b1 levels, as well as with vascular density, in RA synovium. After small interfering RNA transfection or after addition of specific antibodies for CD147, the production of VEGF and HIF\u20101\u03b1 were significantly reduced. The expression of VEGF and HIF\u20101\u03b1 decreased more after CD147 inhibition than after infliximab treatment in the engrafted tissues in SCID\u2010HuRAg mice. The phosphatidylinositol 3\u2010kinase\/Akt pathway may be involved in this process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CD147 induces up\u2010regulation of VEGF and HIF\u20101\u03b1 in RA FLS, further promotes angiogenesis, and leads to the persistence of synovitis. Inhibition of CD147 may be a promising target for novel therapeutic strategies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.34341","type":"journal-article","created":{"date-parts":[[2011,12,14]],"date-time":"2011-12-14T17:23:35Z","timestamp":1323883415000},"page":"1818-1827","source":"Crossref","is-referenced-by-count":57,"title":["CD147 induces angiogenesis through a vascular endothelial growth factor and hypoxia\u2010inducible transcription factor 1\u03b1\u2013mediated pathway in rheumatoid arthritis"],"prefix":"10.1002","volume":"64","author":[{"given":"Cong\u2010hua","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010na","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010feng","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing\u2010yao","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao\u2010hui","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010nan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,5,25]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01661"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199806)41:6<951::AID-ART2>3.0.CO;2-D"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.031641"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380107"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200009)43:9<1905::AID-ANR1>3.0.CO;2-P"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1899"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108291200"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11389"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780371116"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep099"},{"key":"e_1_2_7_13_2","first-page":"1624","article-title":"Role of vascular endothelial growth factor in angiogenesis of rheumatoid arthritis","volume":"22","author":"Nagashima M","year":"1995","journal-title":"J Rheumatol"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.842"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.24844"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1778"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.163"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199807)41:7<1258::AID-ART17>3.0.CO;2-1"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-009-0885-8"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E02-09-0598"},{"key":"e_1_2_7_21_2","first-page":"2276","article-title":"Regulation of MMP\u20101 and MMP\u20102 production through CD147\/extracellular matrix metalloproteinase inducer interactions","volume":"61","author":"Sun J","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_7_22_2","first-page":"333","article-title":"Effects of PMA on CD147 expression in cultured THP\u20101 cells and monocytes of RA patients","volume":"22","author":"Li HM","year":"2006","journal-title":"Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2008.02877.x"}],"container-title":["Arthritis &amp; 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