Vp. Persy et al., Differences in osteopontin up-regulation between proximal and distal tubules after renal ischemia/reperfusion, KIDNEY INT, 56(2), 1999, pp. 601-611
Background. Osteopontin (OPN) is a highly acidic phosphoprotein containing
an arginine-glycine-aspartic acid (RGD) cell adhesion motif. High OPN expre
ssion has been found in tissues with high cell turnover, and OPN up-regulat
ion has been demonstrated in several models of renal injury, suggesting a p
ossible role in tissue remodeling and repair. However, its exact function i
n the kidney remains unknown. In this study, the possible contribution of O
PN to regeneration and repair in the kidney was explored by studying the ti
me course and subcellular localization of OPN up-regulation after renal isc
hemia/reperfusion injury in different nephron segments and by investigating
its relationship with tubular morphology.
Methods. Rats that underwent 60 minutes of left renal ischemia and a right
nephrectomy sacrificed at 10 different time points (from 1 hr to 10 days af
ter reperfusion) were compared with uninephrectomized rats at each time poi
nt. In renal tissue sections immunostained for OPN, proximal (PTs) and dist
al tubules (DTs) in both the renal cortex and outer stripe of the outer med
ulla (OSOM) were scored for the degree of OPN expression and tubular morpho
logy.
Results. Kidneys of uninephrectomized rats showed no injury, and the locali
zation and intensity of their OPN expression remained unaltered compared wi
th normal rats. After ischemia/reperfusion, morphological damage was most s
evere in PTs of the OSOM, but all examined nephron segments showed a signif
icant increase in OPN expression. The time course of OPN up-regulation was
different in PTs and DTs. DTs in both cortex and OSOM rapidly increased the
ir OPN expression, with a maximum at 24 hours after reperfusion followed by
a slow decrease. In contrast, PTs showed a delayed increase in OPN stainin
g, with a maximum after five to seven days, higher in the OSOM than in the
cortex. In OSOM PTs, OPN expression was predominantly associated with morph
ological regeneration, whereas DTs showed a substantial OPN up-regulation w
ithout major morphological damage. PTs and DTs displayed a different subcel
lular OPN staining pattern: OPN staining in DTs was located to the apical s
ide of the cell; PTs, however, presented a vesicular, perinuclear staining
pattern.
Conclusions. Our study found a different pattern of OPN up-regulation after
renal ischemia/reperfusion in PTs versus DTs, both with regard to time cou
rse and subcellular localization. DTs show an early and persistent increase
in OPN staining in the absence of major morphological injury, whereas OPN
staining in PTs is delayed and is mostly associated with morphological rege
neration. PTs show a vesicular, perinuclear OPN staining pattern, whereas D
Ts show OPN staining at the apical cell side.