Cyclooxygenase-2 up-regulation in reflux nephropathy.
OBJECTIVE
Reflux nephropathy (RN) is a major cause of end stage renal failure in children and hypertension is a frequent complication. Cyclooxygenase-2 (COX-2) is an enzyme responsible for the prostaglandin synthesis. It has been shown that COX-2 up-regulates renin production leading to renovascular hypertension. We investigate COX-2 expression in the kidneys of children with RN.


METHODS
Kidney specimens from 12 patients 2 to 13 years old with severe RN secondary to primary high grade vesicoureteral reflux obtained at the time of nephrectomy and 5 controls were examined. Single labeled immunohistochemistry was performed with 2 COX-2 antibodies using light and confocal microscopy. Quantification of COX-2 was determined by Western blotting analysis. COX-2 gene expression was evaluated by real-time quantitative reverse transcription polymerase chain reaction.


RESULTS
There was a strong COX-2 immunoreactivity in the proximal tubules and tubulointerstitial space in the RN samples compared to controls. Immunoreactive COX-2 protein expression was markedly increased in RN samples compared to controls. Real-time reverse transcription polymerase chain reaction showed a significant increase in COX-2 mRNA expression in the RN samples compared to controls (p <0.05).


CONCLUSIONS
Over expression of COX-2 in reflux nephropathy suggests that COX-2 may be involved in the pathogenesis of tubulointerstitial damage associated with severe reflux nephropathy.
D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D051546:Cyclooxygenase 2; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006977:Hypertension, Renal / Q000235:genetics* / Q000473:pathology; D007223:Infant; D007527:Isoenzymes / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000201:enzymology / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D009395:Nephritis, Interstitial / Q000235:genetics* / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000235:genetics; D014718:Vesico-Ureteral Reflux / Q000235:genetics* / Q000473:pathology
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases