Cyclooxygenase-2 expression is associated with the renal macula densa of patients with Bartter-like syndrome.
BACKGROUND
Bartter-like syndrome (BLS) is a heterogeneous set of congenital tubular disorders that is associated with significant renal salt and water loss. The syndrome is also marked by increased urinary prostaglandin E2 (PGE2) excretion. In rodents, salt and volume depletion are associated with increased renal macula densa cyclooxygenase-2 (COX-2) expression. The expression of COX-2 in human macula densa has not been demonstrated. The present studies examined whether COX-2 can be detected in macula densa from children with salt-wasting BLS versus control tissues.


METHODS
The intrarenal distribution of COX-2 protein and mRNA was analyzed by immunohistochemistry and in situ hybridization in 12 patients with clinically and/or genetically confirmed BLS. Renal tissue rejected for transplantation, from six adult patients not affected by BLS, was also examined.


RESULTS
The expression of COX-2 immunoreactive protein was observed in cells of the macula densa in 8 out 11 patients with BLS. In situ hybridization confirmed the expression of COX-2 mRNA in the macula densa in 6 out of 10 cases. COX-2 protein was also detected in the macula densa in a patient with congestive heart failure. The expression of COX-2 immunoreactive protein was not observed in cells associated with the macula densa in kidneys from patients without disorders associated with hyper-reninemia.


CONCLUSIONS
These studies demonstrate that COX-2 may be detected in the macula densa of humans. Since macula densa COX-2 was detected in cases of BLS, renal COX-2 expression may be linked to volume and renin status in humans, as well as in animals.
Kömhoff
M
M
Division of Nephrology, Departments of Medicine and Molecular Physiology and Biophysics, Veterans Administration Medical Center, and Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Jeck
N D
ND
Seyberth
H W
HW
Gröne
H J
HJ
Nüsing
R M
RM
Breyer
M D
MD
D001477:Bartter Syndrome / Q000378:metabolism* / Q000473:pathology; D002648:Child; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics*; D007606:Juxtaglomerular Apparatus / Q000201:enzymology* / Q000473:pathology; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology
D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D012083:Renin; D015232:Dinoprostone