Stress proteins in glomerular epithelial cell injury.
Glomerular visceral epithelial cells (GEC) or podocytes are highly differentiated, specialized cells that play a key role in the maintenance of glomerular permselectivity. Injury of GEC, leading to proteinuria, contributes to the pathogenesis of human and experimental glomerulopathies. Recent studies have demonstrated that stress proteins may be induced and may be involved in the modulation of GEC injury. The C5b-9 membrane attack complex of complement induces GEC injury and proteinuria in the passive Heymann nephritis (PHN) model of membranous nephropathy. C5b-9 induces upregulation of the endoplasmic reticulum (ER) stress proteins, bip and grp94, in part, via activation of cytosolic phospholipase A2. These ER stress proteins limit complement-mediated GEC injury. In experimental nephropathy associated with hyperlipidemia, and in experimental diabetic nephropathy, there is an upregulation of the ER heat shock protein (Hsp) 47, a chaperone protein involved in the synthesis or assembly of collagens. Hsp47 expression in GEC is associated with increased deposition of collagen, and glomerulosclerosis. Hsp27, a stress protein involved in actin polymerization, is localized in GEC, and its expression and activation are increased in the rat puromycin aminonucleoside model of focal segmental glomerulosclerosis, and in PHN. Hsp27 may preserve actin structure, and facilitates survival in the context of injury. Development of methods to induce expression/activation of stress proteins may eventually lead to novel approaches to the therapy of GEC injury and proteinuria.
Bijian
Krikor
K
Department of Medicine, McGill University Health Centre, McGill University, Montreal, Quebec, Canada.
Cybulsky
Andrey V
AV
D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology*; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology*
D006360:Heat-Shock Proteins