Are renal proximal tubular epithelial cells constantly prepared for an emergency? Focus on 'The proliferation capacity of the renal proximal tubule involves the bulk of differentiated epithelial cells'

摘要

A human kidney contains approximately one million functional units (the nephrons) that consist of a filter (the glomerulus) and a processing portion (the proximal, intermediate, and distal tubule). The glomeruli produce -180 liters of primary filtrate every day of which only 1 to 2 liters are finally excreted as urine. It can be easily envisioned that an injury to any portion of the kidney could result in disastrous consequences, and indeed acute renal failure remains a pressing problem in clinical practice and new therapeutic approaches are urgently needed. Theoretically, an injury could strike any part of the nephron, but for reasons only poorly understood the straight portion of the proximal tubule in many cases is most severely affected. Various kinds of injuries may lead to "acute tubular necrosis" (a misnomer because tubular epithelial cells often die by apoptosis), a pathological entity characterized by the loss of tubular epithelial cells and a denuded tubular basement membrane. A number of publications have demonstrated that the proximal tubule can restore its integrity completely. Obviously, however, the regenerative capacity of the proximal tubule sometimes does not suffice or otherwise acute renal failure would not become life threatening. Therefore, one has to wonder whether we can develop strategies to support the regeneration of the tubular epithelium. Under normal circumstances tubular epithelial cells in the adult rat kidney turn over very little, but after an acute injury many mitotic cells have been observed both by proliferating cell nuclear antigen (PCNA) staining (13) and by incorporation of the thymidine analogue bromodeoxyuridine (BrdU) (1). After it was first believed that the surviving epithelial cells dedifferentiate, move through the cell cycle until tubular integrity is restored, go back into Go phase, and redifferentiate, alternative explanations have been put forward such as the existence of resident renal stem cells or the influx of hematopoietic stem cells from the bone marrow. With the publication of the articles by Vogetseder et al. (10-12), it now appears that the pendulum has swung back to the original interpretation.