ENHANCED EXPRESSION OF THE CYTOSKELETAL-ASSOCIATED PROTEIN, PAXILLIN,IN EXPERIMENTAL NEPHROTIC SYNDROME

Background: In the model of aminonucleoside of Puromycin (PAN)-induced nephrotic syndrome we assessed changes in glomerular expression of th ree proteins that regulate cell adhesion to extracellular matrix: paxi llin, focal adhesion kinase (FAK), and Rho, Methods: Following a singl e intravenous injection of PAN in Sprague-Dawley rats, proteinuria ens ued and glomeruli were isolated at three stages: prior to onset of pro teinuria (days 1 and 2), and when proteinuria peaked (day 9), subsided (day 29) or resolved (day 35), Glomerular protein lysates were analyz ed by Western blot for expression of paxillin, FAK, and Rho, Results: There was a progressive increase in glomerular paxillin level that pea ked concomitantly with heavy proteinuria (day 9), Paxillin remained in creased during the recovery phase of PAN-induced injury and when prote inuria resolved. Expression of FAK and Rho remained unchanged at all t ime points. To explore whether the increase in paxillin expression fol lowing administration of PAN was due to a direct effect on glomerular epithelial cells (GEC), cultured rat GECs were incubated with PAN for 3, 6, and 24 hours, and expression of paxillin was assessed in GEC lys ates by Western blot analysis. No change in paxillin levels was observ ed. Conclusions: In PAN-induced nephrotic syndrome there is a preferen tial increase in paxillin expression that cannot be accouted for by an effect of PAN on GEC paxillin synthesis. We propose that the enhanced paxillin synthesis in the course of PAN-induced GEC injury reflects p erturbations in contact between GEC and the GEM and may play a role in regulating adherence of GEC to the GEM.