Localization of proliferating cell nuclear antigen, vimentin, c-Fos, and clusterin in the postischemic kidney. Evidence for a heterogenous genetic response among nephron segments, and a large pool of mitotically active and dedifferentiated cells.

作者：Ralph Witzgall, Dennis J. Brown, Christoph C. Schwarz, Joseph V. Bonventre · 发表于：Journal of Clinical Investigation · 年份：1994 · DOI：10.1172/jci117214 · 被引用次数：612 · 研究领域：Clusterin in disease pathology、Biomarkers in Disease Mechanisms、Trace Elements in Health

The mechanisms leading to the recovery of the kidney after ischemic acute renal failure are poorly understood.To explore the role played by mitogenesis and dedifferentiation in this re- pair process and to identify whether the genetic response of the nephron segments reflects the level of susceptibility to injury, the temporal and nephron segment expressions of various pro- teins implicated in mitogenesis, differentiation, and injury were determined.Proliferating cell nuclear antigen (PCNA), a marker for the G1-S transition in the cell cycle and hence mito- genesis, was detected primarily in the S3 segment of the proxi- mal tubule, with maximal expression at 2 d postischemia.Vimentin, normally present in mesenchymal cells but not epithelial cells, and hence a marker for the state of differentiation, was prominently expressed in the S3 segment 2-5 d postische- mia.In the S3 segments in the outer stripe of the medulla cells that stained positively for PCNA also stained positively for vimentin.Clusterin, a marker for cell injury, was expressed primarily in the S3 segment and in the distal tubule with dis- tinct staining patterns in each segment.None of the cells that stained with clusterin antibodies were positively stained with PCNA or vimentin antibodies.Likewise, none of the PCNA or vimentin-positive cells expressed clusterin at detectable levels.Thus, in the S3 segment, where there is significant ischemic injury, surviving cells express markers indicating that they un- dergo...