P12 PROTEOSTASIS AS A THERAPEUTIC TARGET IN GLOMERULAR INJURY

Injury in glomerulonephritis may be associated with “proteotoxicity” due to protein misfolding, and induction of endoplasmic reticulum (ER) stress and polyubiquitination. Examples include complement-induced glomerular epithelial cell (GEC)/podocyte injury in membranous nephropathy, and focal segmental glomerulosclerosis (FSGS). Podocyte injury due to proteotoxicity can also result from mutations in integral proteins, which lead to their misfolding and accumulation. We assessed if small molecule modulators of proteostasis or accelerated removal of misfolded proteins by the ubiquitin-proteasome system (UPS) can ameliorate the proteotoxicity of misfolded proteins, using GEC culture and in vivo models of glomerular injury.