Anti-dsDNA antibodies induce cell activation and fibronectin synthesis in human renal proximal tubular epithelial cells

Moderated Poster Session: Cell Signaling, Cell Growth Control, Hormones and CytokinesConferenc theme: Sustainability and DiversityINTRODUCTION AND AIMS: Tubulo-interstitial inflammation and fibrosis correlate with renal prognosis. We investigated the role of anti-dsDNA antibodies in the pathogenesis of tubulo-interstitial pathology in lupus nephritis, focusing on their effect on epithelial-to-mesenchymal transition (EMT) and fibrogenesis in renal proximal tubular epithelial cells (PTEC). METHODS: Polyclonal anti-dsDNA antibodies were isolated from the sera of 10 patients with lupus nephritis using affinity chromatography. Confluent, growth-arrested human PTEC were cultured with human polyclonal anti-dsDNA antibodies or control IgG (10 μg/ml for both) for periods up to 48h and synthesis of mediators of cell activation, EMT and fibrosis investigated. RESULTS: Anti-dsDNA antibodies significantly induced synthesis of soluble and insoluble fibronectin in PTEC after 24h incubation (P<0.01 for both). Anti-dsDNA antibodies induced fibroblast specific protein-1 and β-catenin synthesis (P