Renal osteopontin protein and mRNA upregulation during acute nephrotoxicity in the rat

Background. The effect of segment-specific proximal tubular injury on spati o-temporal osteopontin (OPN) distribution was determined in two different n ephrotoxic rat models to evaluate its conceivability with a possible role f or OPN in acute renal failure (ARF). OPN gene expression was further determ ined in proximal and distal tubular cells to investigate the origin of incr eased renal OPN. Methods. Renal OPN protein and mRNA expression were compared in the rat dur ing mercuric-chloride- vs gentamicin-induced ARF using immunohistochemistry and ill situ hybridization. Results. Mercuric chloride primarily induced tubular injury and subsequent cell proliferation in proximal straight tubules (PST), whereas gentamicin p redominantly injured proximal convoluted tubules (PCT). In both models, the distribution of OPN protein was associated with increased OPN mRNA levels in proximal as well as distal tubular cells. However, upregulation was dela yed in the proximal tubular segment suffering most from injury, i.e. PCT in gentamicin ARF vs PST in mercuric-chloride ARF. OPN immunostaining at the apical cell membrane from distal tubules was in contrast to perinuclear ves icular staining in proximal tubular cells. Conclusions. OPN gene and protein expression is induced in both proximal an d distal tubular cells during rat toxic ARF. The distinct subcellular local ization in proximal vs distal tubular cells indicates differences in OPN pr ocessing and/or handling. The spatiotemporal distribution is consistent wit h a possible role ill renal injury and regeneration.