Cyclooxygenase-2 expression in the developing human kidney

Kanwar Nasir M. Khan, Kristina M. Stanfield, Andrew Dannenberg, Surya V. Seshan, Rebecca N. Baergen, David A. Baron, Robert A. Soslow

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)461-466
Number of pages6
JournalPediatric and Developmental Pathology
Volume4
Issue number5
DOIs
StatePublished - Sep 12 2001

Keywords

  • COX-2
  • Fetus
  • Non-steroidal anti-inflammatory drugs
  • Renal

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pathology and Forensic Medicine

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