• Acquired loss of renal nuclease activity is restricted to DNase I and is an organselective feature in murine lupus nephritis 

      Seredkina, Natalya; Rekvik, Ole Petter (Journal article; Tidsskriftartikkel; Peer reviewed, 2011)
      An acquired loss of renal DNaseI has recently been shown to promote transformation of mild mesangial lupus nephritis into membrano-proliferative end-stage organ disease. In this study, we analyzed expression profiles of DNaseI in other organs of lupus-prone (NZBxNZW)F1 mice during disease progression to determine if silencing of the renal DNaseI gene is an organ specific feature or if loss of ...
    • Anti-dsDNA Antibodies Promote Initiation, and Acquired Loss of Renal Dnase1 Promotes Progression of Lupus Nephritis in Autoimmune (NZBxNZW)F1 mice 

      Fenton, Kristin Andreassen; Fismen, Silje; Hedberg, Annica; Seredkina, Natalya; Fenton, Christopher Graham; Mortensen, Elin; Rekvik, Ole Petter (Journal article; Tidsskriftartikkel; Peer reviewed, 2009)
    • IL-1β Promotes a New Function of DNase I as a Transcription Factor for the Fas Receptor Gene 

      Thiyagarajan, Dhivya; Pedersen, Hege Lynum; Seredkina, Natalya; Horvei, Kjersti Daae; Arranz, Lorena; Sonneveld, Ramon; Nijenhuis, Tom; van der Vlag, Johan; Rekvig, Ole Petter (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-02-06)
      Recently we described that endonuclease inactive DNase I translocated into the nucleus in response to increased endogenous IL-1β expression. Here, we demonstrate impact and function of translocated DNase I in tubular cells. Effect of cytokines on expression level and nuclear localisation of DNase I and corresponding levels of Fas receptor (FasR) and IL-1β were determined by confocal microscopy, qPCR ...
    • Lupus nephritis : the role of renal DNase I in the progression of the disease 

      Seredkina, Natalya (Doctoral thesis; Doktorgradsavhandling, 2011-05-31)
      SLE er en sykdom med ukjent etiologi. En hovedmarkør for sykdommen SLE er produskjon av antistoffer mot kroppseget DNA (arvestoff). Binding av slike antistoffer til DNA fører til dannelse av immunkomplekser som i sin tur avleires i organer og bidrar til kliniske symptomer og sykdomsutvikling. I nyrene forårsakes det lekkasje av eggehvite (proteinuri) og er et tegn på alvorlig nyresvikt. Vi ...
    • Lupus nephritis progression in FcγRIIB-/-yaa mice is associated with early development of glomerular electron dense deposits and loss of renal DNase I in severe disease. 

      Horvei, Kjersti Daae; Pedersen, Hege Lynum; Fismen, Silje; Thiyagarajan, Dhivya; Schneider, Andrea; Rekvig, Ole Petter; Winkler, Thomas; Seredkina, Natalya (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-11-30)
      FcγRIIB<sup>-/-</sup>yaa mice develop severe lupus glomerulonephritis due to lack of an inhibitory immune cell receptor combined with a Y-chromosome linked autoimmune accelerator mutation. In the present study, we have investigated nephritis development and progression in FcγRIIB<sup>-/-</sup>yaa mice to find shared features with NZB/NZW F1 lupus prone mice and human disease. We sacrificed 25 male ...
    • Lupus Nephritis: Enigmas, Conflicting Models and an Emerging Concept 

      Seredkina, Natalya; van der Vlag, Johan; Berden, Jo; Mortensen, Elin Synnøve; Rekvig, Ole Petter (Journal article; Tidsskriftartikkel; Peer reviewed, 2013)
      Autoantibodies to components of chromatin, which include double-stranded DNA (dsDNA), histones and nucleosomes, are central in the pathogenesis of lupus nephritis. How anti-chromatin autoantibodies exert their nephritogenic activity, however, is controversial. One model assumes that autoantibodies initiate inflammation when they cross-react with intrinsic glomerular structures such as components ...
    • Lupus nephritis: low urinary DNase I levels reflect loss of renal DNase I and may be utilized as a biomarker of disease progression 

      Pedersen, Hege Lynum; Horvei, Kjersti Daae; Thiyagarajan, Dhivya; Norby, Gudrun; Seredkina, Natalya; Moroni, Gabriella; Eilertsen, Gro Østli; Holdaas, Hallvard; Strøm, Erik Heyerdahl; Bakland, Gunnstein; Meroni, Pier Luigi; Rekvig, Ole Petter (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-02-21)
      Renal DNase I is lost in advanced stages of lupus nephritis. Here, we determined if loss of renal DNase I reflects a concurrent loss of urinary DNase I, and whether absence of urinary DNase I predicts disease progression. Mouse and human DNase I protein and DNase I endonuclease activity levels were determined by western blot, gel, and radial activity assays at different stages of the murine and human ...
    • Silencing of Renal DNaseI in Murine Lupus Nephritis Imposes Exposure of Large Chromatin Fragments and Activation of Toll Like Receptors and the Clec4e 

      Thiyagarajan, Dhivya; Fismen, Silje; Seredkina, Natalya; Jacobsen, Søren; Elung-Jensen, Thomas; Kamper, Anne-Lise; Fenton, Christopher Graham; Rekvig, Ole Petter; Mortensen, Elin Synnøve (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)
      Recent studies demonstrate that transformation of mild lupus nephritis into end-stage disease is imposed by silencing of renal DNaseI gene expression in (NZBxNZW)F1 mice. Down-regulation of DNaseI results in reduced chromatin fragmentation, and in deposition of extracellular chromatin-IgG complexes in glomerular basement membranes in individuals that produce IgG anti-chromatin antibodies. The main ...
    • TNFα amplifies DNaseI expression in renal tubular cells while IL-1β promotes nuclear DNaseI translocation in an endonuclease-inactive form 

      Thiyagarajan, Dhivya; Rekvig, Ole Petter; Seredkina, Natalya (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-06-11)
      We have demonstrated that the renal endonuclease DNaseI is up-regulated in mesangial nephritis while down-regulated during progression of the disease. To determine the basis for these reciprocal DNaseI expression profiles we analyse processes accounting for an early increase in renal DNaseI expression. Main hypotheses were that i. the mesangial inflammation and secreted pro-inflammatory cytokines ...