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Loss of imprinting of IGF2 characterizes high IGF2mRNA-expressing type of Fibroblast-like Synoviocytes in Rheumatoid Arthritis
  1. Alejandro Martin-Trujillo (a.martin_trujillo{at}vumc.nl)
  1. VU University Medical Center, Netherlands
    1. Johanna G I van Rietschoten (jgi.vanrietschoten{at}vumc.nl)
    1. VU University Medical Center, Netherlands
      1. Trieneke C G Timmer (t.timmer{at}vumc.nl)
      1. VU University Medical Center, Netherlands
        1. Francisco Milena Rodriguez
        1. VU University Medical Center, Netherlands
          1. Tom W J Huizinga (t.w.j.huizinga{at}lumc.nl)
          1. Leiden University Medical Center, Netherlands
            1. Paul-Peter Tak (p.p.tak{at}amc.uva.nl)
            1. AMC Amsterdam, Netherlands
              1. Sara Marsal (smarsal{at}ir.vhebron.net)
              1. Institut de Recerca Vall d'Hebron, Hospital Universitari Vall d'Hebron, Spain
                1. Saleh M Ibrahim (saleh.ibrahim{at}med.uni-rostock.de)
                1. University of Rostock, Germany
                  1. Ben A C Dijkmans (bac.dijkmans{at}vumc.nl)
                  1. VU University Medical Center, Netherlands
                    1. Tineke C T M van der Pouw Kraan (t.vanderpouwkraan{at}vumc.nl)
                    1. VU University Medical Center, Netherlands
                      1. Cornelis L Verweij (c.verweij{at}vumc.nl)
                      1. VU University Medical Center, Netherlands

                        Abstract

                        Objective: Increased expression of insulin-like growth factor 2 (IGF2) by fibroblast-like synoviocytes (FLS) was associated with low inflammatory synovium of patients with rheumatoid arthritis (RA). The aim of this study was to analyze whether the differential expression of IGF2, whose expression is normally restricted to one allele, is due to activation of the normally suppressed allele.

                        Methods: IGF2 gene expression of RA FLS was quantified by quantitative RT-PCR. FLS heterozygous for a 3’UTR IGF2 polymorphism were selected to measure the relative contribution of the allelic transcripts by allele-specific transcript quantification assay. Proliferation was determined by [3H]-Thymidine incorporation.

                        Results: IGF2 was shown to contribute to RA FLS proliferation. FLS could be classified in IGF2 high- and IGF2 low-expressing cell lines. Here we report that allelic IGF2 transcript quantification analysis revealed that in part of the RA FLS the normally suppressed allele was activated, resulting in biallelic expression of the IGF2 gene. Biallelic expression was associated with increased levels of IGF2 mRNA production.

                        Conclusion: Our findings indicate that the imprinting status of IGF2 might underlie increased expression of IGF2 that may contribute to autonomous growth of RA FLS of low inflammatory synovial tissues.

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