Deletion of cyclooxygenase (COX)-2 causes impairment of kidney development, including hypothrophic glomeruli and cortical thinning. A critical role for COX-2 is seen 4–8 days postnatally. The present study was aimed at answering whether different COX-2 gene dosage and partial pharmacological COX-2 inhibition impairs kidney development. We studied kidney development in COX-2+/+, COX-2+/−, and COX-2−/− mice as well as in C57Bl6 mice treated postnatally with low (5 mg·kg−1·day−1) and high (10 mg·kg−1·day−1) doses of the selective COX-2 inhibitor SC-236. COX-2+/− mice exhibit impaired kidney development leading to reduced glomerular size but, in contrast to COX-2−/− mice, only marginal cortical thinning. Moreover, in COX-2+/− and COX-2−/− kidneys, juxtamedullary glomeruli, which develop in the very early stages of nephrogenesis, also showed a size reduction. In COX-2+/− kidneys at the age of 8 days, we observed significantly less expression of COX-2 mRNA and protein and less PGE2 and PGI2 synthetic activity compared with COX-2+/+ kidneys. The renal defects in COX-2−/− and COX-2+/− kidneys could be mimicked by high and low doses of SC-236, respectively. In aged COX-2+/− kidneys, glomerulosclerosis was observed; however, in contrast to COX-2−/− kidneys, periglomerular fibrosis was absent. COX-2+/− mice showed signs of kidney insufficiency, demonstrated by enhanced serum creatinine levels, quite similar to COX-2−/− mice, but, in contrast, serum urea remained at the control level. In summary, function of both COX-2 gene alleles is absolutely necessary to ensure physiological development of the mouse kidney. Loss of one copy of the COX-2 gene or partial COX-2 inhibition is associated with distinct renal damage and reduced kidney function.
- kidney development
- Copyright © 2016 the American Physiological Society
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