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norskBlar i forfatter Det helsevitenskapelige fakultet "Thiyagarajan, Dhivya"
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IL-1β Promotes a New Function of DNase I as a Transcription Factor for the Fas Receptor Gene
(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 progression in FcγRIIB-/-yaa mice is associated with early development of glomerular electron dense deposits and loss of renal DNase I in severe disease.
(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: low urinary DNase I levels reflect loss of renal DNase I and may be utilized as a biomarker of disease progression
(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 ... -
Progressive lupus nephritis : biological consequences of renal DNaseI gene silencing
(Doctoral thesis; Doktorgradsavhandling, 2013-10-11)Systemic lupus erythematous (SLE) is an autoimmune syndrome which occurs most often between the ages 10-50 years. Lupus nephritis is the most severe clinical manifestation of SLE. 30-60% of the SLE patients may develop lupus nephritis during lifetime. At a certain time point in the life of (NZBxNZW) F1 mice prone to develop lupus nephritis, the expression of renal DNaseI endonuclease is lost. This ... -
Silencing of Renal DNaseI in Murine Lupus Nephritis Imposes Exposure of Large Chromatin Fragments and Activation of Toll Like Receptors and the Clec4e
(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
(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 ...
