ALTERED EXPRESSION OF GLOMERULAR HEAT-SHOCK PROTEIN-27 IN EXPERIMENTAL NEPHROTIC SYNDROME

Although nephrotic syndrome is a very common kidney disease, little is known about the molecular changes occurring within glomerular capilla ry loops during development of disease, The characteristic histologic change is retraction (effacement) of the distal ''foot'' processes of glomerular epithelial cells (GEC) which surround the capillary loops. The GEC foot processes are an essential part of the kidney's filtratio n barrier, and their structure is regulated primarily by actin microfi laments, cytoskeletal proteins present in high concentrations in foot processes, Actin polymerization has been reported to be regulated via phosphorylation of the low molecular weight heat shock protein, hsp27. We localized hsp27 within normal rat GECs using immunofluorescence an d immunoelectron microscopy. Induction of nephrotic syndrome and GEC f oot process effacement using the puromycin aminonucleoside rat model r esulted in significant increases in: (a) renal cortical hsp27 mRNA exp ression (826+/-233%, x+/-SEM, P < 0.01 vs. control); (b) glomerular hs p27 protein expression (87+/-2%, P < 0.001 vs. control); and (c) glome rular hsp27 phosphorylation (101+/-32%, P < 0.05 vs, control). These f indings support the hypothesis that hsp27, by regulating GEC foot proc ess actin polymerization, may be important in maintaining normal foot process structure, and regulating pathophysiologic GEC cytoskeletal ch anges during development of nephrotic syndrome.