The Fas ligand/Fas system in renal injury.
The FasL-Fas system regulates renal cell apoptosis, as well as the immune and inflammatory responses. Evidence that FasL and Fas participate in renal injury may be summarized along modified Koch's postulates (Table 1): (i) FasL is expressed by renal cells and during renal injury, (ii) activation of the Fas receptor promotes apoptosis of cultured renal cells, (iii) Fas agonists induce glomerular injury but they may also decrease renal injury by limiting injurious immunological responses, (iv) mice with disrupted FasL/Fas systems are protected from tubular cell injury during ischaemia reperfusion, although they develop autoimmune glomerulonephritis if other genetic predisposing factors are present. FasL/Fas must be considered a new target for therapeutic intervention in renal injury. Therapeutic modulation of Fas should aim not only at protecting intrinsic glomerular or tubular epithelial cells from death, but also at modulating the immune, inflammatory, and fibrogenic responses. Possible therapeutic interventions include Fas agonists, soluble Fas receptors, or other antagonists, and targetting of Fas to undesired cells, such as fibroblasts, in order to decrease their numbers in a physiological manner through apoptosis. Any therapeutic attempt should carefully take into account the possible effects of interference with Fas in other 1833 cell systems. Given the complexities of the FasL/Fas system, further studies are warranted.
Ortiz
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Lorz
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Egido
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J
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053222:Fas Ligand Protein; D006801:Humans; D007674:Kidney Diseases / Q000503:physiopathology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D019463:Mice, Inbred MRL lpr / Q000502:physiology; D009154:Mutation / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D019014:fas Receptor / Q000502:physiology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor