Cyclooxygenase-2 expression in the developing human kidney.

TitleCyclooxygenase-2 expression in the developing human kidney.
Publication TypeJournal Article
Year of Publication2001
AuthorsKhan KN, Stanfield KM, Dannenberg A, Seshan SV, Baergen RN, Baron DA, Soslow RA
JournalPediatr Dev Pathol
Date Published2001 Sep-Oct
KeywordsCyclooxygenase 2, Embryonic and Fetal Development, Gestational Age, Humans, Immunoenzyme Techniques, Isoenzymes, Kidney, Membrane Proteins, Prostaglandin-Endoperoxide Synthases

Cyclooxygenase (COX) exists in two related but unique isoforms, COX-1 and COX-2, and is suggested to have specific functions in different segments of the nephron. COX-2 knockout mice develop fatal nephropathy, which implies that this isoform is important during nephrogenesis. The histologic changes seen in the COX-2 knockout mice are similar to those observed in the kidneys of human fetuses exposed to non-steroidal anti-inflammatory drugs (NSAIDs) in the third trimester of pregnancy. However, only minimal amounts of COX-2 mRNA or protein have been reported in the adult human kidney. We hypothesized that expression of COX-2 is significant in the fetal human kidney and that it is involved in the development of the nephron. To characterize the presence of COX-2 in the human fetal kidney, we used immunohistochemistry to evaluate its expression in 23 fetal kidneys ranging between 15 and 23 weeks of gestational age. Strong expression of COX-2 was localized primarily in the macula densa and the thick ascending limb of the loop of Henle, and in rare glomerular podocytes and vascular endothelial cells. There was a progressive decrease in COX-2 immunoreactivity from the most immature nephrons adjacent to the metanephric regions to the well-developed nephrons in the middle to inner cortex. In contrast to the adult human kidney, this temporal and spatial expression of COX-2 in the fetal kidney suggests that this enzyme may be involved in nephrogenesis, and its inhibition by NSAIDs during the third trimester may be responsible for fetal renal syndromes.

Alternate JournalPediatr Dev Pathol
PubMed ID11779048
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