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Cycloxygenase-2 Is Expressed in Vasculature of Normal and Ischemic Adult Human Kidney and Is Colocalized with Vascular Prostaglandin E₂ EP4 Receptors

Karina L. Therland^*, Jane Stubbe^*, Helle C. Thiesson^*, Peter D. Ottosen, Steen Walter, Grith L. Sørensen, Ole Skøtt^* and Boye L. Jensen^*

*Department of Physiology and Pharmacology, Department of Immunology and Microbiology, University of Southern Denmark, and Institute of Pathology, Department of Urology, Odense University Hospital, Odense, Denmark.

Correspondence to Dr. Boye L. Jensen, Department of Physiology and Pharmacology, University of Southern Denmark, Winsløwparken 21, 3, DK-5000, Odense C, Denmark. Phone: +45-65-50-37-96; Fax +45-66-13-34-79; E-mail bljensen{at}health.sdu.dk

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 E₂ synthase (PGES) in collecting ducts, and PGES was also detected in macula densa cells. Vascular COX-2 was colocalized with prostaglandin E₂ 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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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673