Glomerular osteopontin expression and macrophage infiltration in glomerulosclerosis of DOCA-salt rats

Expression of the chemoattractant osteopontin (OPN) may contribute to macro phage infiltration in many types of tubulointerstitial kidney disease, but the role of OPN in chronic glomerulosclerosis is unknown. We hypothesized t hat glomerular OPN expression and macrophage infiltration occur in deoxycor ticosterone acetate (DOCA)-salt glomerulosclerosis in rats, Uninephrectomiz ed rats receiving DOCA pellets and 1% saline were compared with control rat s, OPN mRNA was determined by Northern blot, and OPN protein was determined by Western blot. The localization of OPN was studied by in situ hybridizat ion and double immunohistochemistry with glomerular cell markers. Macrophag e infiltration was quantified by counting ED-1-positive cells, and semiquan titative glomerulosclerosis scores were obtained. In DOCA-salt rats, OPN mR NA in the kidney was increased 2-fold over control after 9 days and 3 weeks and 20-fold after 6 weeks. Tubulointerstitial OPN staining was apparent af ter 21 days of DOCA treatment. Glomerular OPN mRNA and protein was detected after 42 days in parietal and visceral epithelial cells, activated myofibr oblasts, and occasionally mesangial cells, Progressive glomerular macrophag e infiltration occurred during the development of DOCA hypertension, parall eling the degree of glomerulosclerosis. Glomeruli staining positive for ost eopontin contained more macrophages (18.4 +/- 3.4 per cross-section) than o steopontin-negative glomeruli (3.6 +/- 0.5; P < 0.05). Glomerular OPN expre ssion occurs in chronic hypertensive glomerulosclerosis and is associated w ith macrophage Infiltration, The data suggest a role for OPN as a chemoattr actant in hypertensive glomerulosclerosis, (C) 2001 by the National Kidney Foundation, Inc.