Tubulointerstitial disease in glomerulonephritis. Potential role of osteopontin (uropontin)

Interstitial inflammation and tubular injury accompany most types of glomerulonephritis and are likely to mediate progressive renal injury. We hypothesized that the interstitial monocyte/macrophage accumulation in nephritis involves osteopontin, a cell attachment glycoprotein that avidly binds macrophages in vitro and induces a macrophage-rich infiltrate on subcutaneous injection in mice (Singh et al, J Exp Med, 1990, 171: 1931). In this study, we demonstrate that osteopontin messenger RNA and protein levels are up-regulated in a proportion of proximal and distal tubules in three experimental models of glomerulonephritis. In all three models, the expression of osteopontin initially precedes histological evidence of tubular injury, but is correlated with subsequent sites of monocyte/macrophage accumulation and tubular damage. Osteopontin expression also correlates with the severity of the tubulointerstitial injury, being greatest in amino-nucleoside nephrosis. These data suggest that 1) osteopontin is up-regulated in tubules in glomerular disease; 2) osteopontin may be important for macrophage accumulation at specific sites in diseased tissue; and 3) osteopontin may therefore have a role in the pathogenesis of the tubulointerstitial injury that accompanies glomerulonephritis.