{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:53:56Z","timestamp":1790870036065,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,2,5]],"date-time":"2004-02-05T00:00:00Z","timestamp":1075939200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2004,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine novel genes regulated by tumor necrosis factor \u03b1 (TNF\u03b1) signaling in primary rheumatoid arthritis synovial fibroblasts (RASFs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Oligonucleotide microarrays were used to measure gene expression levels in 6 independent replicate samples of RASFs. RASFs were transfected for 18 hours with AdI\u03baB\u2013dominant negative (AdI\u03baB\u2010DN) (n = 3) or with control AdTet expressing the reverse tetracycline <jats:italic>trans<\/jats:italic>\u2010activator (n = 3). The cells were stimulated for 3 hours with TNF\u03b1, and total RNA was prepared. Several novel parametric and nonparametric methods were used to rank genes in terms of the magnitude and significance of intergroup differences. Microarray expression differences were confirmed by real\u2010time quantitative reverse transcription\u2013polymerase chain reaction. Small interfering RNA (siRNA) was used to specifically down\u2010modulate microarray\u2010identified genes to demonstrate their role in the promotion of apoptosis, proliferation, or matrix metalloproteinase (MMP) expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Blocking of NF\u2010\u03baB by AdI\u03baB\u2010DN was associated with a down\u2010modulation of antiapoptosis genes, including BIRC\u20103, and several novel genes, including GG2\u20101, a TNF\u03b1\u2010inducible FLIP\u2010like gene. Other families of genes that were significantly down\u2010regulated by AdI\u03baB\u2010DN included cytokines\/chemokines (interleukin\u20101\u03b2 [IL\u20101\u03b2], IL\u20108, IL\u201015, and RANTES), adhesion molecule (vascular cell adhesion molecule 1, intercellular adhesion molecule 1), and unique genes that have not previously been reported to be regulated by TNF\u03b1 in RA. Inhibition of the GG2\u20101 gene using the siRNA technique resulted in significantly enhanced apoptosis, decreased proliferation, and decreased production of MMP\u20101 in TNF\u03b1\u2010stimulated RASFs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These studies provide a comprehensive analysis of genes that are differentially regulated by TNF\u03b1 signaling and NF\u2010\u03baB nuclear translocation in RASFs and demonstrate methods for confirming the expression and functional significance of such genes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.20037","type":"journal-article","created":{"date-parts":[[2004,2,9]],"date-time":"2004-02-09T18:29:18Z","timestamp":1076351358000},"page":"420-431","source":"Crossref","is-referenced-by-count":53,"title":["Novel tumor necrosis factor \u03b1\u2013regulated genes in rheumatoid arthritis"],"prefix":"10.1002","volume":"50","author":[{"given":"Huang\u2010Ge","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karren","family":"Hyde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grier P.","family":"Page","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob P. 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