Work

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.

Year: 1994

Type: article

Abstract: 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 mitogenesis and dedifferentiate in the postischemic pe- riod.While there is some expression of c-Fos in the S3 seg- ment, c-Fos was expressed predominantly, at 1 and 3 h postischemia, in the nuclei of the distal nephron, particularly in the thick ascending limb.The data support the view that the ma- ture renal S3 segment epithelial cell can be a progenitor cell.(J.Clin.Invest.1994.93:2175-2188.) Key words: acute renal fail- ure * gene expression -ischemia -kidney -tissue repair Proliferating cell nuclear antigen (PCNA), I a DNA polymer- ase 6-associated protein, was used as a marker for cell prolifera- tion.PCNA-labeled nuclei identify a population of cells in late GI and early S phases ofthe cell cycle (10).Vimentin was used as a marker of differentiation.Vimentin is an intermediate filament protein that is expressed in mesenchymal tissue but not in normal differentiated kidney epithelial cells.The expres- sion pattern of c-Fos, the product of the c-fos immediate-early gene, was also evaluated.This gene is induced in a number of 1. Abbreviation used in this paper: PCNA, proliferating cell nuclear antigen.

Source: Journal of Clinical Investigation

DOI: 10.1172/jci117214

Authors: R Witzgall, D Brown, C Schwarz, J V Bonventre

Institutions: Harvard University, Massachusetts General Hospital, Harvard–MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology

Language: English

Topic: Acute Kidney Injury Research

Subfield: Nephrology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke