Role of Fas (CD95) in tubulointerstitial disease induced by unilateral ureteric obstruction.
Murine renal tubular epithelial cells and interstitial fibroblasts may express both Fas (CD95) death receptor and Fas ligand and are vulnerable to Fas-mediated death in vitro. We therefore hypothesized that an absence of renal Fas may protect resident cells from undergoing apoptosis. We performed unilateral ureteric ligation [producing unilateral ureteral obstruction (UUO)] in 6-wk-old normal control mice and C57Bl6/lpr mice, which express a nonfunctional Fas receptor. Obstructed kidneys were removed at days 3, 7, and 14 (n = 6 per group). Tubular cell apoptosis at day 7 was significantly reduced in lpr mice [21.8 +/- 5.8 vs. 45.7 +/- 7.6 cells/10 high-power fields (hpf), P < 0.02]. Importantly, there was no difference in tubular cell proliferation between normal and lpr mice at any time point studied. Interestingly, double labeling with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and the proximal tubule-specific antibody Fx1A indicated that the absence of Fas reduced distal but not proximal tubular death at day 7. In addition, there was no difference in interstitial cell apoptosis or proliferation, suggesting that Fas does not play a significant role in interstitial cell death. Importantly, inflammatory macrophage infiltration and ultimate collagen I deposition was unchanged in lpr mice. In conclusion, the absence of functional cell surface Fas in UUO provides distal tubular cells with partial protection from apoptosis but does not affect interstitial cell fate in this model of tubulointerstitial injury.
Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington 98195, USA. jeremyh@u.washington.edu
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Hughes
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Johnson
D000818:Animals; D016923:Cell Death; D007668:Kidney / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009395:Nephritis, Interstitial / Q000209:etiology* / Q000473:pathology; D014517:Ureteral Obstruction / Q000150:complications*; D019014:fas Receptor / Q000502:physiology*
D019014:fas Receptor