Human urine contains several macromolecules which inhibit calcium oxalate c
rystallization. Osteopontin (or uropontin), a secreted phosphoglycoprotein
with the amino acid sequence Arg-Gly-Asp (RGD) and high affinity to hydroxy
apatite, is one such inhibitor. To investigate the action of this protein o
n renal stone formation, the expression osteopontin gene in normal and chem
ically induced urolithiasis rat kidney was compared at both mRNA and protei
n levels. Northern blot analysis shown a significant increase of osteoponti
n mRNA level in stone-forming rat kidney compared with normal ones. In an i
n situ hybridization study, we localized the transcripts of the osteopontin
gene in epithelial cells of both distal and collective tubules, and found
a remarkably strong signal in stone-forming rats. The amount and distributi
on of the protein in kidney from immunocytochemistry staining showed the sa
me pattern as seen in situ hybridization. These findings indicate that oste
opontin may be an important macromolecule in the normal endogenous defence
against the formation of urinary calculi.