title: Distal tubular epithelial cells of the kidney: Potential support for proximal tubular cell survival after renal injury.
abstract: The tubular epithelium of the kidney is susceptible to injury from many causes, such as ischemia-reperfusion and the associated oxidative stress, nephrotoxins, inflammatory and immune disorders and many others. The outcome is often acute kidney injury, which may progress to chronic kidney disease and fibrosis. Acute kidney injury involves not only direct injury to the distal tubular (DT) and proximal tubular (PT) epithelium during and immediately following the injurious event, but the closely-associated and sometimes dysfunctional renal vascular endothelium also plays an important part in modulating the tubular epithelial injury. In comparison with the PT, the DT epithelium is less sensitive to cell death, especially after ischemic injury. It is more prone to apoptosis than necrosis when it dies, and has key paracrine and autocrine functions in secreting an array of inflammatory, reparative, and survival cytokines that include chemotactic cytokines, polypeptide growth factors, and vasoactive peptides. In a neighborly way, the cytokines and growth factors secreted by the DT epithelium may then act positively on the ischemia-sensitive PT that has receptors to many of these proteins, but may not be able to synthesize them. A more complete understanding of these cellular events will allow protection against nephron destruction, regeneration leading to re-epithelialization of the injured tubules, or prevention of progression to chronic kidney disease. This review looks at these functions in the DT epithelial cells, specifically the cells in the medullary thick ascending limb of the loop of Henle, in contrast with those of the straight segment of the PT.
authors.affiliation: Molecular and Cellular Pathology, School of Medicine, University of Queensland, Herston 4006, Australia. g.gobe@uq.edu.au
authors.forename: Glenda C
authors.initials: GC
authors.lastname: Gobe
authors.forename: David W
authors.initials: DW
authors.lastname: Johnson
mesh_terms: D000818:Animals; D002470:Cell Survival; D004847:Epithelial Cells / Q000166:cytology*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007674:Kidney Diseases / Q000473:pathology*; D007686:Kidney Tubules, Distal / Q000166:cytology*; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000473:pathology*
chemical_list: D006360:Heat-Shock Proteins