Effects Of Glucocorticoid On The Expression Of C-Jun And C-Fos In T Cells Of Children With Idiopathic Nephrotic Syndrome

BackgroundIdiopathic nephrotic syndrome(INS)is a common glomerular disease in childhood.At present,Glucocorticoid(GC)is the main treatment in the clinic,but patients have different responses to GC,some are sensitive to GC,some patients are sensitive to GC,but the disease is repeated during the process of GC reduction,and GC appears.Resistance,but what causes this group of patients to develop steroid resistance? The reasons and mechanisms are still not very clear.Because of steroid-resistant INS patients,renal dysfunction is much faster than hormone-sensitive INS patients,and may eventually develop into end-stage renal disease.Therefore,studying the mechanism of hormonal resistance is one of the hot issues in the field of kidney disease research.At present,studies have shown that the activation of activator protein-1(AP-1)is closely related to hormone resistance.However,the specific mechanism is still unclear.This topic is intended to do some exploratory work in this area.ObjectiveTo investigate the molecular mechanism of glucocorticoid resistance by detecting the effects of glucocorticoids on the expression of c-Jun and c-Fos genes in peripheral blood T cells of children with idiopathic nephrotic syndrome.MethodsA total of 49 children with idiopathic nephrotic syndrome were selected,48 of whom were glucocorticoid sensitive and 1 of whom was glucocorticoid resistant with recurrent disease after the urine protein was conversed to negative.First of all,2 ml of peripheral venous blood was respectively extracted from the selected INS children at 3 time points,namely before GC treatment,after GC treatment of urinary protein turned negative,before INS recurrence and before GC drug resistant retreatment.Immunomagnetic beads were used to isolate T cells.On the other hand,the peripheral blood T cells of 1 hormone-resistant child with recurrence after GC treatment who received re-treatment were detected by mRNA expression profiling(Shanghai Qualcomm Biotechnology Co,Ltd.,Affymetrix GeneChip Gene 2.0 Array)at 3 time points.The expression of c-Jun and c-Fos genes in the peripheral blood T cells was detected by QPCR at 2 time points before and after GC treatment of urinary protein in 48 hormone-sensitive children.Result1.One case of INS initial treatment of urinary protein was relieved,and the disease recurred and rectified to produce glucocorticoid resistance children.The microarray analysis of related gene mRNA expression showed that there were 300 genes in peripheral blood T cells,and the genes with larger changes were c-Fos,c-Jun;and compared with before GC treatment,GC-treated genes with significantly increased expression of urinary protein after negative conversion were c-Jun,c-Fos,and the expression levels were increased by 12-fold and 11-fold,respectively;Compared with before GC treatment,the genes with recurrence of INS and significantly increased expression of glucocorticoid resistance have platelet basic protein gene(PPBP),G protein signal transduction regulator 18(RSG18),c-Jun,c-Fos,etc.Where in the expression of c-Jun and c-Fos increased by 7 times and 5 times,respectively.2.The results of QPCR in 48 children with glucocorticoid resistance INS showed that the levels of c-Jun and c-Fos gene expression in peripheral blood T cells were significantly higher after GC treatment than before treatment(P < 0.01).ConclusionGlucocorticoid therapy increases c-Jun and c-Fos gene expression in peripheral blood T cells of children with INS,which may be related to hormone resistance to INS.One of the reasons for delayed hormone resistance in children may be the increased expression of c-Jun and c-Fos induced by GC.