Expression of osteopontin in gentamicin-induced acute tubular necrosis andits recovery process

Background. There is controversy regarding the exact localization and roles of osteopontin (OPN), a multipotential chemokine, in renal injury. There i s little information on the expression and role of OPN in gentamicin-induce d acute tubular necrosis (ATN) and its recovery process. Methods. A severe ATN model was made using male Wistar rats by injecting ge ntamicin (150 mg/kg/day) for five days and limiting the provision of water. The expression and localization of OPN mRNA and protein, ED1 as a macropha ge marker, proliferating cellular nuclear antigen (PCNA), CD44 as an OPN re ceptor, megalin as a proximal tubule marker, and their relationships to eac h other were examined from the early tubular necrotic period to the late re covery period by Northern blotting, in situ hybridization, and double immun ohistochemical staining. Results. In the gentamicin group, OPN mRNA and protein were expressed in on ly the PCNA-positive proliferating cortical distal tubules, not in the necr otic proximal tubules, until day 6 after the first administration, but were found markedly in PCNA-positive regenerative proximal and distal tubules o n days 10, 15, and 30. The localization of PCNA-positive cells was almost a lways accompanied with the up-regulated expression of OPN using quantitativ e analysis (P < 0.01). CD44 expression was markedly up-regulated in the ren al cortical tubular epithelium from days 6 to 30. In the control group, no expression of OPN and CD44 in the cortical area was found throughout the ex perimental period. Conclusions. These results suggested that OPN is related to the proliferati on and regeneration of tubular epithelial cells after tubular damage.