Induction and altered localization of 90-kDa heat-shock protein in rat kidneys with cisplatin-induced acute renal failure.

We purified 90-kDa heat-shock protein (HSP90) from murine brains and produced a specific antibody against the protein in a rabbit. This antibody cross-reacted with rat renal HSP90 on immunoblot analysis. Using the antibody, we observed serial immunohistochemical localizations of HSP90 in rat kidneys with cisplatin-induced acute renal failure. In normal kidneys, HSP90 was mainly localized in the cytoplasm of distal tubules and collecting ducts. Twenty-four hours after the cisplatin exposure, a rapid expression of HSP90 was observed in the cytoplasm of epithelial cells in the Henle's loops (especially at the luminal side), although there was little change in these cells on light microscopy. Degenerative changes of epithelial cells appeared in the S3 segment of proximal tubules on day 3, and epithelial cell regeneration in this portion was found from day 5. On day 5, HSP90 was markedly expressed in both the cytoplasm and the nucleus of epithelial cells in the S3 segment with a granular pattern. The induced HSP90 was then accumulated in the cytoplasm of these cells on day 7 and disappeared on day 14. Immunoblot analysis of isotonic buffer-extractable renal fractions showed that there was a rapid induction of HSP90 from day 1, and that the maximum induction of HSP90 in the extract at day 5 was 6-fold that of a control. These results suggest that HSP90 plays some role related to functional abnormalities of the Henle's loops at the luminal side, and in the regeneration of damaged cells in the S3 segment of proximal tubules, during the course of cisplatin-induced acute tubular injury.