Immunohistochemical study of heat shock protein 27 with respect to survival and regeneration of proximal tubular cells after uranyl acetate-induced acute tubular injury in rats

Abstract

This study examined the possible role of heat shock protein 27 (HSP27) expression in the survival and regeneration of proximal tubule (PT) cells after acute tubular injury. Rats were injected with a low (0.2 mg/kg) or high (4 mg/kg) dose of uranyl acetate (UA) to induce renal injury. Renal tissues were immunostained for HSP27, focal adhesion kinase (FAK), and bromodeoxyuridine (BrdU), and stained by the TUNEL method. Low-dose UA induced focal PT depletion in the proximal three-quarters of the S3 segment. Here, cells became sporadically positive for cytoplasmic HSP27 in association with FAK+, and almost all BrdU+ early regenerating cells were positive for HSP27 from days 2 to 3. High-dose UA induced severe PT depletion in the proximal three-quarters of S3, and a small number of PT cells became positive for HSP27 as early as day 2. BrdU+, early regenerating cells were restricted to the distal quarter of S3 from days 2 to 3, with or without HSP27 staining and with FAK. In both groups, HSP+ PT cells and BrdU+ cells peaked in number at day 5. The PT cells showed reduced HSP27 accumulation by day 7 as they differentiated, but remained immunopositive for FAK. TUNEL+ apoptotic cells were immunonegative for both HSP27 and FAK. Cytoplasmic HSP27 accumulation in PT cells seems to contribute to PT survival and transition from PT cell proliferation to differentiation. When PT cells are severely impaired, distinct cells in the distal areas of S3 could undergo cell cycle progression without HSP27 accumulation.