{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T23:14:31Z","timestamp":1770506071062,"version":"3.49.0"},"reference-count":19,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Physiological Genomics"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:p> Recently clusterin (CLU) was reported to be an inhibitor of NF-\u03baB pathway and involved in rheumatoid arthritis (RA) synovitis. This study was designed to decipher the molecular network linked to CLU expression in FLS (fibroblast-like synoviocytes) and evaluate the consequences of its low expression in conditions of TNF-\u03b1 stimulation. FLS were transfected with siRNA for CLU or not and cultured for 24 and 48 h with TNF-\u03b1 or not. Pan-genomic gene expression was assayed by DNA microarray. The gene network around CLU and gene interactions were analyzed with the Ingenuity Pathway Analysis software. Downregulation of CLU resulted in modification of the expression of genes known to be directly linked to CLU and for almost 5% of the tested genes (857 out of 17,225); the upregulation of a small group of gene (e.g., TIAM1) emphasizes the hypothetical role of CLU in the pseudotumoral characteristic of FLS. The comparison of gene expression with or without TNF stimulation allowed the classification of sampled with good concordance. Moreover, differential comparison showed that CLU downregulation in RA led to a profound modification of the TNF-\u03b1 response as three sets of genes emerged: 497 genes modulated by siCLU transfection with TNF stimulation, 356 genes modified because of TNF stimulation only, and 484 genes modulated during TNF stimulation with CLU expression (e.g., IL-8 and Wnt signaling genes). Using a global two-way ANOVA we could identify a set of genes defining a molecular signature of TNF response directly influenced by CLU. These results (based on differential gene expression patterns) argue that CLU downregulation in FLS alters their aggressiveness in RA synovitis. <\/jats:p>","DOI":"10.1152\/physiolgenomics.00095.2010","type":"journal-article","created":{"date-parts":[[2011,12,14]],"date-time":"2011-12-14T05:16:30Z","timestamp":1323839790000},"page":"229-235","source":"Crossref","is-referenced-by-count":8,"title":["Implication of clusterin in TNF-\u03b1 response of rheumatoid synovitis: lesson from in vitro knock-down of clusterin in human synovial fibroblast cells"],"prefix":"10.1152","volume":"44","author":[{"given":"G\u00e9raldine","family":"Falgarone","sequence":"first","affiliation":[{"name":"Sorbonne Paris Cit\u00e9, University of Paris 13, EA-4222;"},{"name":"Assistance Publique - H\u00f4pitaux de Paris, H\u00f4pital Avicenne, Rheumatology Department, Bobigny;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdellatif","family":"Essabbani","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), U1016, Institut Cochin, D\u00e9partement d'Immunologie-H\u00e9matologie;"},{"name":"Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 8104;"},{"name":"Universit\u00e9 Paris Descartes;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florent","family":"Dumont","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 8104;"},{"name":"Universit\u00e9 Paris Descartes;"},{"name":"INSERM, U1016, Institut Cochin, Plateforme g\u00e9nomique, Paris;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Cagnard","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), U1016, Institut Cochin, D\u00e9partement d'Immunologie-H\u00e9matologie;"},{"name":"Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 8104;"},{"name":"Universit\u00e9 Paris Descartes;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvie","family":"Mistou","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), U1016, Institut Cochin, D\u00e9partement d'Immunologie-H\u00e9matologie;"},{"name":"Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 8104;"},{"name":"Universit\u00e9 Paris Descartes;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilles","family":"Chiocchia","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), U1016, Institut Cochin, D\u00e9partement d'Immunologie-H\u00e9matologie;"},{"name":"Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 8104;"},{"name":"Universit\u00e9 Paris Descartes;"},{"name":"Service de rhumatologie, H\u00f4pital Ambroise Par\u00e9, Universit\u00e9 de Versailles-Saint-Quentin, Boulogne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"B1a","doi-asserted-by":"publisher","DOI":"10.1002\/art.23968"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-7-73"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00619"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.9.6471"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364132"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C109.057133"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(09)04008-1"},{"key":"B8","first-page":"11","volume":"15","author":"Fujinami M","year":"1997","journal-title":"Clin Exp Rheumatol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1126\/science.1137306"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209233200"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nri2094"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1023\/B:BREA.0000018421.31632.e6"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2007.10.005"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C300252200"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302265"},{"key":"B15a","author":"Tamhane AC","year":"2000","journal-title":"Statistics and Data Analysis: From Elementary to Intermediate"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1297.033"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-2664"}],"container-title":["Physiological Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/physiolgenomics.00095.2010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T00:09:19Z","timestamp":1567987759000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/physiolgenomics.00095.2010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2]]},"references-count":19,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2012,2]]}},"alternative-id":["10.1152\/physiolgenomics.00095.2010"],"URL":"https:\/\/doi.org\/10.1152\/physiolgenomics.00095.2010","relation":{},"ISSN":["1094-8341","1531-2267"],"issn-type":[{"value":"1094-8341","type":"print"},{"value":"1531-2267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2]]}}}