A. Hartner et al., Glomerular osteopontin expression and macrophage infiltration in glomerulosclerosis of DOCA-salt rats, AM J KIDNEY, 38(1), 2001, pp. 153-164
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.