Chondroitin sulfate degradation and eicosanoid metabolism pathways are impaired in focal segmental glomerulosclerosis: experimental confirmation of an in silico prediction

Focal segmental glomerulosclerosis (FSGS), the most common primary glomerular disease, is a diverse clinical entity that occurs after podocyte injury. Although numerus studies suggested molecular pathways responsible for development of FSGS, many unknowns still remain about its pathogenic mechanism. Two important pathways were predicted as candidates for pathogenesis of FSGS in our previous in silico analysis that we aim to confirm these pathways experimentally in the present study. The expression level of four enzyme genes that are representative of "chondroitin sulfate degradation" and "eicosanoid metabolism" pathways were investigated in the urinary sediment of biopsy proven FSGS patients and healthy subjects using real-time polymerase chain reaction (RT-PCR). These target genes were arylsulfatase, hexosaminidase, cyclooxygenase-2 and prostaglandin I2 synthase. The patients were sub-divided into two groups based on range of proteinuria and glomerular filtration rate and were compared for variation in the expression of target genes. Correlation of target genes with clinical and pathological characteristics of the disease was calculated and receiver operating characteristic (ROC) analysis was performed. A combined panel of arylsulfatase, hexosaminidase and cyclooxygenase-2 improved the diagnosis of FSGS to 76%. Hexosaminidase was correlated with the level of proteinuria, while cyclooxygenase-2 was correlated with interstitial inflammation and serum creatinine level in the disease group. Our data supported the implication of these target genes and pathways in the pathogenesis of FSGS. Besides, these genes can also be considered as non-invasive biomarkers for FSGS.