title: Identification of genes regulating TRAIL-induced apoptosis in rheumatoid arthritis fibroblasts-like synoviocytes.
abstract: We previously described that sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis varied in rheumatoid arthritis fibroblasts-like synoviocytes (RAFLS) from one patient to another and was correlated with disease severity. Therefore, we screened for genes differentially expressed in RAFLS sensitive and resistant to TRAIL-induced apoptosis. The sensitivity of RAFLS was defined based on the percentage of TRAIL-induced apoptosis: 0-10% for resistant cells and >25% for sensitive RAFLS. We performed transcriptomic comparison between RAFLS-S (n=6) and RAFLS-R (n=6) and then examined the implication of identified candidates in the regulation of apoptosis using small interference RNA (siRNA). Microarray analysis revealed 10 functional genes differentially expressed according to TRAIL sensitivity. These factors are implicated in different functions, such as the respiratory chain (ND3), the transport of lipids (OSBP2, PLTP), the regulation of signaling linked to extracellular factors (SULF2, GALNT1, SIAE) or the regulation of gene expression (TET2 and LARP6). We confirmed differential expression for GALNT1 and LARP6 by quantitative reverse transcriptase-PCR. Using siRNA extinction, we demonstrated the implication of GALNT1, SULF2 and LARP6 in the control of TRAIL-induced responses. These results are of particular interest as GALNT1 and LARP6 have been implicated in the regulation of cell death and may represent interesting targets to induce apoptosis of RAFLS.
authors.affiliation: Department of Rheumatology, Lapeyronie Hospital and Montpellier University, Montpellier, France.|Institut de Génétique Moléculaire de Montpellier, CNRS, UMR 5535 Montpellier, France.
authors.forename: R
authors.initials: R
authors.lastname: Audo
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, CNRS, UMR 5535 Montpellier, France.
authors.forename: A
authors.initials: A
authors.lastname: Hegglin
authors.affiliation: MGX-Montpellier GenomiX, Montpellier, France.
authors.forename: D
authors.initials: D
authors.lastname: Severac
authors.affiliation: MGX-Montpellier GenomiX, Montpellier, France.
authors.forename: C
authors.initials: C
authors.lastname: Dantec
authors.affiliation: Department of Rheumatology, Lapeyronie Hospital and Montpellier University, Montpellier, France.|Institut de Génétique Moléculaire de Montpellier, CNRS, UMR 5535 Montpellier, France.
authors.forename: B
authors.initials: B
authors.lastname: Combe
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, CNRS, UMR 5535 Montpellier, France.|Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Hahne
authors.affiliation: Department of Rheumatology, Lapeyronie Hospital and Montpellier University, Montpellier, France.|Institut de Génétique Moléculaire de Montpellier, CNRS, UMR 5535 Montpellier, France.
authors.forename: J
authors.initials: J
authors.lastname: Morel
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*
chemical_list: D034741:RNA, Small Interfering; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human