NOX-mediated impairment of PDGF-induced DNA synthesis in peripheral blood lymphocytes of children with idiopathic nephrotic syndrome.

BackgroundCellular oxidative stress, inflammatory responses, and immunogenic events are involved in pathogenesis of idiopathic nephrotic syndrome (INS); however, the exact mechanism remains unknown. We examined NADPH oxidase (NOX) activity and platelet-derived growth factor (PDGF)-induced DNA synthesis in peripheral blood lymphocytes (PBL) of patients with INS.MethodsPBL from 15 patients with INS and 15 age- and gender-matched controls were isolated, and enzyme activities of NOX, catalase, and superoxide dismutase (SOD) were measured along with the assay of malondialdehyde levels and bromo-deoxyuridine incorporation. Protein expression of NOX-1 was measured using western blot analysis.ResultsPatients with INS had significantly (P<0.01) higher NOX activity and increased protein expression of NOX-1 in PBL as compared with controls. Catalase and SOD activities were markedly lower with lipid peroxide levels significantly (P<0.01) increased in patients with INS. Ex vivo DNA synthesis in PDGF-stimulated PBL was significantly (P<0.01) reduced in patients with INS; however, diphenyliodonium, an inhibitor of NOX, markedly corrected impairment in growth factor-induced BrdU incorporation.ConclusionsThese results show that NOX activation might have a role in regulation of lymphocytic activity in patients with INS through the impairment of PDGF mitogenic function and might contribute toward pathogenesis of nephrotic syndrome.