Expression of mediators of renal injury in the remnant kidney of ROP mice is attenuated by cyclooxygenase-2 inhibition.

Cheng H, Zhang M, Moeckel GW, Zhao Y, Wang S, Qi Z, Breyer MD, Harris RC
Nephron Exp Nephrol. 2005 101 (3): e75-85

PMID: 15995341 · DOI:10.1159/000086645

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.

Copyright 2005 S. Karger AG, Basel.

MeSH Terms (17)

Animals Connective Tissue Growth Factor Cyclooxygenase 2 Inhibitors Fibronectins Glomerulosclerosis, Focal Segmental Immediate-Early Proteins Intercellular Signaling Peptides and Proteins Kidney Kidney Tubules Mice Mice, Inbred Strains Nephrectomy Proteinuria Proto-Oncogene Proteins c-met Pyrazoles Sulfonamides Tissue Distribution

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