Abstract:
:Rheumatoid arthritis is a chronic inflammatory disease with a high prevalence and substantial socioeconomic burden. Despite intense research efforts, its aetiology and pathogenesis remain poorly understood. To identify novel genes and/or cellular pathways involved in the pathogenesis of the disease, we utilized a well-recognized tumour necrosis factor-driven animal model of this disease and performed high-throughput expression profiling with subtractive cDNA libraries and oligonucleotide microarray hybridizations, coupled with independent statistical analysis. This twin approach was validated by a number of different methods in other animal models of arthritis as well as in human patient samples, thus creating a unique list of disease modifiers of potential therapeutic value. Importantly, and through the integration of genetic linkage analysis and Gene Ontology-assisted functional discovery, we identified the gelsolin-driven synovial fibroblast cytoskeletal rearrangements as a novel pathophysiological determinant of the disease.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Aidinis V,Carninci P,Armaka M,Witke W,Harokopos V,Pavelka N,Koczan D,Argyropoulos C,Thwin MM,Möller S,Waki K,Gopalakrishnakone P,Ricciardi-Castagnoli P,Thiesen HJ,Hayashizaki Y,Kollias Gdoi
10.1371/journal.pgen.0010048keywords:
subject
Has Abstractpub_date
2005-10-01 00:00:00pages
e48issue
4eissn
1553-7390issn
1553-7404journal_volume
1pub_type
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