Cited 14 time in webofscience Cited 16 time in scopus

Identification of key regulators for the migration and invasion of rheumatoid synoviocytes through a systems approach

Title
Identification of key regulators for the migration and invasion of rheumatoid synoviocytes through a systems approach
Authors
You, S[You, Sungyong]Yoo, SA[Yoo, Seung-Ah]Choi, S[Choi, Susanna]Kim, JY[Kim, Ji-Young]Park, SJ[Park, Su-Jung]Ji, JD[Ji, Jong Dae]Kim, TH[Kim, Tae-Hwan]Kim, KJ[Kim, Ki-Jo]Cho, CS[Cho, Chul-Soo]Hwang, D[Hwang, Daehee]Kim, WU[Kim, Wan-Uk]
DGIST Authors
Hwang, D[Hwang, Daehee]
Issue Date
2014-01-07
Citation
Proceedings of the National Academy of Sciences of the United States of America, 111(1), 550-555
Type
Article
Article Type
Article
Keywords
Arthritis, RheumatoidCell Adhesion MoleculesCell InvasionCell MigrationCell MovementChronic InflammationCluster AnalysisFibroblastsGene Expression ProfilingGene Expression RegulationHumansInflammationInterleukin-1 BetaIntracellular Signaling Peptides and ProteinsLIM Domain ProteinsMacrophagesModels, BiologicalNuclear ProteinsOsteoarthritisPriority JournalProteinProtein ExpressionProtein Twist1Rheumatoid ArthritisSynovial MembraneSynoviocyteSynovitisSystems BiologySystems TheoryTranscription Factor RUNX2TranscriptomeTwist Transcription FactorUnclassified Drug
ISSN
0027-8424
Abstract
Rheumatoid synoviocytes, which consist of fibroblast-like synoviocytes (FLSs) and synovial macrophages (SMs), are crucial for the progression of rheumatoid arthritis (RA). Particularly, FLSs of RA patients (RA-FLSs) exhibit invasive characteristics reminiscent of cancer cells, destroying cartilage and bone. RA-FLSs and SMs originate differently from mesenchymal and myeloid cells, respectively, but share many pathologic functions. However, the molecular signatures and biological networks representing the distinct and shared features of the two cell types are unknown. We performed global transcriptome profiling of FLSs and SMs obtained from RA and osteoarthritis patients. By comparing the transcriptomes, we identified distinct molecular signatures and cellular processes defining invasiveness of RA-FLSs and proinflammatory properties of RA-SMs, respectively. Interestingly, under the interleukin-1β (IL-1β)-stimulated condition, the RA-FLSs newly acquired proinflammatory signature dominant in RA-SMs without losing invasive properties. We next reconstructed a network model that delineates the shared, RA-FLS-dominant (invasive), and RA-SM-dominant (inflammatory) processes. From the network model, we selected 13 genes, including periostin, osteoblast-specific factor (POSTN) and twist basic helix-loop-helix transcription factor 1 (TWIST1), as key regulator candidates responsible for FLS invasiveness. Of note, POSTN and TWIST1 expressions were elevated in independent RA-FLSs and further instigated by IL-1β. Functional assays demonstrated the requirement of POSTN and TWIST1 for migration and invasion of RA-FLSs stimulated with IL-1β. Together, our systems approach to rheumatoid synovitis provides a basis for identifying key regulators responsible for pathological features of RA-FLSs and -SMs, demonstrating how a certain type of cells acquires functional redundancy under chronic inflammatory conditions.
URI
http://hdl.handle.net/20.500.11750/3129
DOI
10.1073/pnas.1311239111
Publisher
National Academy of Sciences
Related Researcher
  • Author Hwang, Dae Hee Systems Biology and Medicine Lab
  • Research Interests Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
Files:
There are no files associated with this item.
Collection:
New BiologyETC1. Journal Articles


qrcode mendeley

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE