Abstract |
The study was performed to elucidate the distribution and cellular localization of cyclooxygenase (COX)-2 in human kidney and to address localization of downstream targets for COX-derived prostanoids. Cortex and outer and inner medulla tissue were obtained from control kidneys ( cancer specimens), kidneys with arterial stenosis, and kidneys of patients who received angiotensin II inhibition or acetylsalicylic acid. Ribonuclease protection assay and Western blot test revealed that COX-1 and -2 mRNA and protein were expressed in all regions of human kidney ( mRNA ratio, cortex:outer medulla:inner medulla COX-1 1:3:20 and COX-2 1:1:3). In adult kidney, immunohistochemical labeling for COX-2 was associated with smooth muscle cells in pre- and postglomerular vessels and with endothelium, particularly in vasa recta and medullary capillaries. Western blot test confirmed COX-2 expression in renal artery. COX-2 had a similar localization in fetal kidney and was additionally observed in Henle's loop and macula densa. Human tissue arrays displayed COX-2 labeling of vascular smooth muscle in multiple extrarenal tissues. Vascular COX-2 expression was significantly increased in kidneys with arterial stenosis. COX-1 was colocalized with microsomal prostaglandin E(2) synthase (PGES) in collecting ducts, and PGES was also detected in macula densa cells. Vascular COX-2 was colocalized with prostaglandin E(2) EP4 receptors but not with EP2 receptors. Thus, renovascular COX-2 expression was a constitutive feature encountered in human kidneys at all ages, whereas COX-2 was seen in macula densa only in fetal kidney. Vascular COX-2 activity in human kidney and extrarenal tissues may support blood flow and affect vascular wall-blood interaction.
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Authors | Karina L Therland, Jane Stubbe, Helle C Thiesson, Peter D Ottosen, Steen Walter, Grith L Sørensen, Ole Skøtt, Boye L Jensen |
Journal | Journal of the American Society of Nephrology : JASN
(J Am Soc Nephrol)
Vol. 15
Issue 5
Pg. 1189-98
(May 2004)
ISSN: 1046-6673 [Print] United States |
PMID | 15100359
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Enzyme Inhibitors
- Isoenzymes
- Membrane Proteins
- PTGER4 protein, human
- RNA, Messenger
- Receptors, Prostaglandin E
- Receptors, Prostaglandin E, EP4 Subtype
- Angiotensin II
- Cyclooxygenase 2
- PTGS2 protein, human
- Prostaglandin-Endoperoxide Synthases
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Topics |
- Adult
- Angiotensin II
(antagonists & inhibitors)
- Cells, Cultured
- Cyclooxygenase 2
- Endothelium, Vascular
(cytology, embryology, enzymology)
- Enzyme Inhibitors
(pharmacology)
- Fetus
- Gene Expression Regulation, Developmental
(drug effects, physiology)
- Humans
- Immunohistochemistry
- Ischemia
(physiopathology)
- Isoenzymes
(antagonists & inhibitors, genetics, metabolism)
- Kidney
(blood supply, embryology)
- Membrane Proteins
- Prostaglandin-Endoperoxide Synthases
(genetics, metabolism)
- RNA, Messenger
(analysis)
- Receptors, Prostaglandin E
(genetics, metabolism)
- Receptors, Prostaglandin E, EP4 Subtype
- Renal Artery Obstruction
(metabolism, physiopathology)
- Umbilical Arteries
(cytology, embryology, enzymology)
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