TUBULOINTERSTITIAL DISEASE IN GLOMERULONEPHRITIS - POTENTIAL ROLE OF OSTEOPONTIN (UROPONTIN)

Interstitial inflammation and tabular injury accompany most types of g lomerulonephritis and are likely to mediate progressive renal injury. We hypothesized that the interstitial monocyte/ macrophage accumulatio n in nephritis involves osteopontin, a cell attachment glycoprotein th at avidly binds macrophages in vitro and induces a macrophage-rich inf iltrate 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 a nd 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 subseq uent sites of monocyte/macrophage accumulation and tubular damage. Ost eopontin expression also correlates with the severity of the tubuloint erstitial injury, being greatest in amino-nucleoside nephrosis. These data suggest that 1) osteopontin is up-regulated in tubules in glomeru lar disease; 2) osteopontin may be important for macrophage accumulati on at specific sites in diseased tissue; and 3) osteopontin may theref ore have a role in the pathogenesis of the tubulointerstitial injury t hat accompanies glomerulonephritis.