Role of renal epithelial cells in the initiation of calcium oxalate stones.
Normal urinary environment is inhibitory to crystallization. Occasional crystals are internalized by the renal epithelial cells and sequestered to lysosomes or externalized into the interstitium to be handled by the inflammatory cells. Elevated levels of oxalate and calcium oxalate crystals, however, provoke renal cells to increase the synthesis of osteopontin, bikunin, heparan sulfate proteoglycan, monocyte chemoattractant protein-1, and prostaglandin E(2), which are known mediators of the inflammatory processes and extracellular matrix production. Osteopontin and bikunin are also modulators of crystallization. Exposed renal epithelial cells are often injured and go through apoptosis and/or necrosis initiating a cascade of events leading to further crystallization, crystal retention and development of stone nidi. Reactive oxygen species are produced during the interactions between the oxalate/crystals and renal cells and are responsible for the various cellular responses. Calcium oxalate crystal deposition in the rat kidneys also activates the renin-angiotensin system. Both oxalate and calcium oxalate crystals selectively activate p38 mitogen-activated protein kinase in the exposed tubular cells. Extracellular environment changes from one that inhibits crystal nucleation, growth, aggregation and retention to that, which promotes these processes.
Khan
Saeed R
SR
Department of Pathology, College of Medicine, University of Florida, Gainesville 32610-0275, USA. khan@pathology.ufl.edu <khan@pathology.ufl.edu>
D000818:Animals; D002129:Calcium Oxalate / Q000378:metabolism*; D002462:Cell Membrane / Q000502:physiology; D049109:Cell Proliferation; D003460:Crystallization; D004195:Disease Models, Animal; D004705:Endocytosis; D004847:Epithelial Cells / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D007668:Kidney / Q000166:cytology* / Q000502:physiology; D007669:Kidney Calculi / Q000503:physiopathology*; D015398:Signal Transduction
D002129:Calcium Oxalate