Background and aims Anti-dsDNA antibody plays a critical role in the pathogenesis of lupus nephritis and contributes to inflammatory and fibrotic processes in the kidney. EDA+ spliced variant of fibronectin (EDA+ FN), normally only weakly expressed, is markedly increased in pathological conditions. We investigated the effect of human polyclonal anti-dsDNA antibodies on the expression of EDA+ FN in proximal tubular epithelial cells (PTEC) and the functional consequence.
Methods EDA+ FN expression in human renal biopsies of Class III/IV±V lupus nephritis was assessed by cytochemistry. Cultured PTEC were incubated with control IgG or IgG anti-dsDNA antibodies isolated from lupus nephritis patients for 24 hour and the expression of EDA+ FN was investigated. Recombinant human EDA peptide was used to investigate the functional role of EDA+ FN in PTEC.
Results The results showed that EDA+ FN was absent from normal kidney tissue but was markedly increased in the tubulo-interstitium in lupus nephritis patients. Cultured PTEC constitutively expressed native FN but not EDA+ FN. Anti-dsDNA antibodies, compared with serum-free-medium and control IgG, increased EDA+ FN expression by 5.8- and 5.6-fold respectively (p<0.05 for both), and the induction was mediated through PI3K and mTOR activation. Exogenous IL-1β and TGF-β1, but not IL-6, IL-8 or MCP-1, induced EDA+ FN by 1.8- and 2.3-fold respectively. Recombinant EDA peptide increased native FN, collagen I, laminin and SNAIL expression, but decreased E-cadherin expression, in PTEC.
Conclusions Our data demonstrated a role of EDA+ FN in the pathogenesis of tubulo-interstitial disease in lupus nephritis.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.