Expression of mediators of renal injury in the remnant kidney of ROP mice is
attenuated by cyclooxygenase-2 inhibition.
Authors Cheng H, Zhang M, Moeckel GW, Zhao Y, Wang S, Qi Z, Breyer MD, Harris RC
Submitted By Raymond Harris on 11/6/2007
Status Published
Journal Nephron. Experimental nephrology
Year 2005
Date Published 8/1/2005
Volume : Pages 101 : e75 - 85
PubMed Reference 15995341
Abstract To investigate the effects of cyclooxygenase-2 (COX-2) inhibition on renal
injury of mice, ROP mice were subjected to subtotal ablation ('remnant'). A
subset of the remnant group was treated with a selective COX-2 inhibitor,
SC58236, in the drinking water. At 12 weeks the remnant group developed
significant albuminuria (181.3 +/- 15.8 microg/24 h), which was blunted by
SC58236 treatment (138.9 +/- 17.1; p < 0.05 compared to remnant). SC58236 did
not alter systemic blood pressure or GFR significantly. Immunoreactive COX-2 was
upregulated in remnant (1.88 +/- 0.35 fold sham, n = 8, p < 0.05), which was
blunted by SC58236 (to 1.26 +/- 0.31 fold sham). Collagen IV mRNA increased
significantly in remnant kidneys (2.69 +/- 0.34 fold sham, n = 8, p < 0.05), and
this increase was inhibited by SC58236 treatment (to 1.84 +/- 0.32 fold
control). Immunoreactive TGF-beta1, connective tissue growth factor, HGF
receptor, c-Met, and fibronectin all increased in remnant (2.85 +/- 0.51, 3.83
+/- 0.55, 2.56 +/- 0.31, and 2.80 +/- 0.39 fold sham respectively, n = 4-8, p <
0.05), and SC58236 blunted the increases (to 1.45 +/- 0.34, 1.85 +/- 0.13, 1.75
+/- 0.30, and 1.60 +/- 0.32 fold sham). Immunohistochemistry indicated that the
major localization for these progression factors was in the tubulointerstitium,
especially in the scar area, which is in agreement with the expression of a
macrophage marker, F4/80. Therefore, these results indicate that in a mouse
model of subtotal renal ablation, COX-2 inhibition blocks expression of
mediators of renal tubulointerstitial injury.


Investigators with authorship
NameInstitution
Matthew BreyerEli Lilly and Company
Raymond HarrisVanderbilt University

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