Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis

Wiley - Tập 58 Số 4 - Trang 1001-1009 - 2008
Joanna Stańczyk1, Deena M. Leslie Pedrioli2, Fabia Brentano1, Olga Sánchez‐Pernaute1, Christoph Kolling3, Renate E. Gay, Michael Detmar2, Steffen Gay, Diego Kyburz1
1Zurich Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland
2Swiss Federal Institute of Technology (ETH Zurich), Zurich, Switzerland#TAB#
3Schulthess Clinic, Zurich, Switzerland

Tóm tắt

AbstractObjectiveMicroRNAs (miRNA) have recently emerged as a new class of modulators of gene expression. In this study we investigated the expression, regulation, and function of miR‐155 and miR‐146a in rheumatoid arthritis (RA) synovial fibroblasts (RASFs) and RA synovial tissue.MethodsLocked nucleic acid microarray was used to screen for differentially expressed miRNA in RASFs treated with tumor necrosis factor α (TNFα). TaqMan‐based real‐time polymerase chain reaction was applied to measure the levels of miR‐155 and miR‐146a. Enforced overexpression of miR‐155 was used to investigate the function of miR‐155 in RASFs.ResultsMicroarray analysis of miRNA expressed in RASFs treated with TNFα revealed a prominent up‐regulation of miR‐155. Constitutive expression of both miR‐155 and miR‐146a was higher in RASFs than in those from patients with osteoarthritis (OA), and expression of miR‐155 could be further induced by TNFα, interleukin‐1β, lipopolysaccharide, poly(I‐C), and bacterial lipoprotein. The expression of miR‐155 in RA synovial tissue was higher than in OA synovial tissue. Enforced expression of miR‐155 in RASFs was found to repress the levels of matrix metalloproteinase 3 (MMP‐3) and reduce the induction of MMPs 3 and 1 by Toll‐like receptor ligands and cytokines. Moreover, compared with monocytes from RA peripheral blood, RA synovial fluid monocytes displayed higher levels of miR‐155.ConclusionThis study provides the first description of increased expression of miRNA miR‐155 and miR‐146a in RA. Based on these findings, we postulate that the inflammatory milieu may alter miRNA expression profiles in resident cells of the rheumatoid joints. Considering the repressive effect of miR‐155 on the expression of MMPs 3 and 1 in RASFs, we hypothesize that miR‐155 may be involved in modulation of the destructive properties of RASFs.

Từ khóa


Tài liệu tham khảo

10.1016/S0092-8674(04)00045-5

10.1038/nrg1990

10.1038/ng1798

10.1016/j.tcb.2006.12.007

10.1186/1471-2164-8-166

10.1038/nature03315

10.1038/ng1536

10.1016/j.devcel.2006.09.009

10.1038/nrc1997

10.1016/j.smim.2005.01.001

10.1016/j.cmet.2006.05.009

10.1038/nm1582

10.1016/j.cell.2007.03.008

10.1084/jem.20061692

10.1371/journal.pone.0000610

10.1002/gcc.20282

10.1073/pnas.0610983104

10.1126/science.1139253

10.1126/science.1141229

Muller‐Ladner U, 1996, Synovial fibroblasts of patients with rheumatoid arthritis attach to and invade normal human cartilage when engrafted into SCID mice, Am J Pathol, 149, 1607

10.1097/01.bor.0000218947.42730.dd

10.1002/art.1780310302

10.1261/rna.2332406

Griffiths‐Jones S, 2006, miRBase: the microRNA sequence database, Methods Mol Biol, 342, 129

10.1093/nar/gni178

10.1016/j.cellimm.2005.04.018

10.1136/ard.61.11.975

Miyazawa K, 1998, Constitutive transcription of the human interleukin‐6 gene by rheumatoid synoviocytes: spontaneous activation of NF‐κB and CBF1, Am J Pathol, 152, 793

10.1073/pnas.0605298103

10.1073/pnas.0500613102

10.1016/S0008-8749(02)00506-3

10.1002/gcc.10186

10.1146/annurev.genom.8.080706.092424

10.1182/blood-2006-12-062398

10.1002/path.1825

10.1158/0008-5472.CAN-05-1783

10.1002/ijc.22394

10.1073/pnas.0610731104

10.1002/art.21273

10.1073/pnas.0602266103

10.1074/jbc.M601496200

10.4049/jimmunol.179.8.5082

Thông tin
Thông tin xuất bản

Wiley

Tập 58 Số 4

1001-1009

Thông tin tác giả