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5-Lipoxygenase and leukotriene A4 hydrolase expression in primary nephrotic syndrome
1Department of Pediatrics, Mansoura University Children's Hospital, Mansoura, Egypt. ashbakr@mans.edu.eg
Insights
Children with active primary nephrotic syndrome (PNS) show gene expression of 5-lipoxygenase (5-LO) and leukotriene A(4) (LTA(4)) hydrolase. These leukotrienes may contribute to PNS but not steroid treatment response in children.
Area of Science:
- Biochemistry
- Pediatric Nephrology
- Molecular Biology
Background:
- Primary nephrotic syndrome (PNS) is a kidney disorder affecting children.
- Leukotrienes are implicated in inflammatory processes, but their role in PNS is not fully understood.
Purpose of the Study:
- To investigate the gene expression of 5-lipoxygenase (5-LO) and leukotriene A(4) (LTA(4)) hydrolase in children with PNS.
- To determine the association between enzyme expression, disease activity, and steroid responsiveness.
Main Methods:
- Analysis of 5-LO and LTA(4) hydrolase gene expression in peripheral blood mononuclear cells (PBMN) from children with active PNS, remission, and controls.
- Utilized reverse transcription and polymerase chain reaction (PCR) for gene amplification.
Main Results:
- All children with active PNS expressed both 5-LO and LTA(4) hydrolase, unlike controls.
- A positive correlation was found between proteinuria levels and the expression of both enzymes in active PNS.
- Enzyme expression did not differ between steroid-sensitive (SSNS) and steroid-resistant (SRNS) PNS patients.
Conclusions:
- Leukotrienes likely play a role in the pathogenesis of childhood PNS.
- Leukotriene pathway enzymes do not appear to be involved in the therapeutic response to steroids in pediatric PNS.
Abstract:
Gene expression of 5-lipoxygenase (5-LO) and leukotriene A(4) (LTA(4)) hydrolase was analyzed in the peripheral blood of 48 children with active primary nephrotic syndrome (PNS) (group I), 27 children with PNS in remission (group II), and 20 controls. Group I included 34 patients with steroid-sensitive PNS (SSNS) and 14 patients with steroid-resistant PNS (SRNS). Total RNA purified from peripheral blood mononuclear (PBMN) cells was reverse transcribed into cDNA and amplified with specific primers in the polymerase chain reaction. All group I patients and none of the controls expressed 5-LO and LTA(4 )hydrolase. Of group II children, 22.2% expressed 5-LO, while 51.9% expressed LTA(4 )hydrolase. Among group I patients there was a significant positive correlation between the degree of proteinuria and the expression of 5-LO ( r=0.27, P=0.03) and LTA(4 )hydrolase ( r=0.44, P=0.001). There was no difference in the degree of expression of both enzymes between SSNS and SRNS patients. In conclusion, leukotrienes may play a role in the pathogenesis of PNS in children, but they do not participate in the response of these patients to steroids.
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