anti-dsdna antibodies promote initiation, and acquired loss of renal dnase1 promotes progression of lupus nephritis in autoimmune (nzbxnzw)f1 miceanti-dsdna抗体促进起始,获得损失狼疮肾炎肾dnase1促进发展的自身免疫性(nzbxnzw)f1小鼠.pdfVIP

Anti-dsDNA Antibodies Promote Initiation, and Acquired Loss of Renal Dnase1 Promotes Progression of Lupus Nephritis in Autoimmune (NZBxNZW)F1 Mice 1. 3. 1 1 5 Kristin Fenton , Silje Fismen , Annica Hedberg , Natalya Seredkina , Chris Fenton , Elin Synnøve Mortensen2,3, Ole Petter Rekvig1,4* 1 Department of Biochemistry, Institute of Medical Biology, Medical Faculty, University of Tromsø, Tromsø, Norway, 2 Department of Pathology, Institute of Medical Biology, Medical Faculty, University of Tromsø, Tromsø, Norway, 3 Department of Pathology, University Hospital of Northern Norway, Tromsø, Norway, 4 Department of Rheumatology, University Hospital of Northern Norway, Tromsø, Norway, 5 The Microarray Platform, Medical Faculty, University of Tromsø, Tromsø, Norway Abstract Background: Lupus nephritis is characterized by deposition of chromatin fragment-IgG complexes in the mesangial matrix and glomerular basement membranes (GBM). The latter defines end-stage disease. Methodology/Principals: In the present study we determined the impact of antibodies to dsDNA, renal Dnase1 and matrix metalloprotease (MMP) mRNA levels and enzyme activities on early and late events in murine lupus nephritis. The major focus was to analyse if these factors were interrelated, and if changes in their expression explain basic processes accounting for lupus nephritis. Findings: Early phases of nephritis were associated with chromatin-IgG complex deposition in the mesangial matrix. A striking observation was that this event correlated with appearance of anti-dsDNA antibodies and mild or clinically silent nephritis. These events preceded down-regulation of renal Dnase1. Later, renal Dnase1 mRNA level and enzyme activity were reduced, while MMP2 mRNA