title: Cyclooxygenase-2 expression in the developing human kidney.
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.
authors.affiliation: Department of Metabolism and Safety Evaluation, Pharmacia, Skokie, IL 60077, USA.
authors.forename: K N
authors.initials: KN
authors.lastname: Khan
authors.forename: K M
authors.initials: KM
authors.lastname: Stanfield
authors.forename: A
authors.initials: A
authors.lastname: Dannenberg
authors.forename: S V
authors.initials: SV
authors.lastname: Seshan
authors.forename: R N
authors.initials: RN
authors.lastname: Baergen
authors.forename: D A
authors.initials: DA
authors.lastname: Baron
authors.forename: R A
authors.initials: RA
authors.lastname: Soslow
mesh_terms: D051546:Cyclooxygenase 2; D005314:Embryonic and Fetal Development; D005865:Gestational Age; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis*; D007668:Kidney / Q000737:chemistry / Q000196:embryology / Q000201:enzymology*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases