FC 029PODOCYTE AND GLOMERULAR ENDOTHELIAL CELL DERIVED MICRORNAS REGULATE PODOCYTE NEPHRONECTIN IN MEMBRANOUS GLOMERULONEPHRITIS

Abstract Background and Aims Autoantibodies binding to podocyte antigens cause idiopathic membranous glomerulonephritis (iMGN). However, it remains elusive how autoantibodies reach the subepithelial space because glomerular filtration barrier is normally size selective impermeable for antibodies. Method Kidney biopsies from patients with MGN, cell culture, zebrafish mice models were used investigate role of nephronectin (NPNT) regulating microRNAs (miRs) barrier. Results We found that endothelial cell-derived miR-192-5p podocyte-derived miR-378a-3p are upregulated in anti-phospholipase A2 receptor antibody positive (PLA2R-ab+) iMGN regulate NPNT expression (Fig. 1). Overexpression as well morpholino mediated npnt knockdown induced edema, proteinuria, loss markers effacement. The most prominent phenotype however structural changes basement membrane (GBM) increased lucidity, slicing lamellation especially lamina rara interna 2, Fig. 3). was comparable ultrastructural findings seen iMGN. IgG sized nanoparticles accumulated lucidity areas densa GBM models. Loss slit diaphragm proteins severe impairment further confirmed specific Npnt knockout 4). Conclusion Podocyte important proper filter function structure regulated by derived miRs. hypothesize part pathophysiology enables immune complex deposition