The Significance Of AP-1 And GR In Steroid Resistant Nephrotic Syndrome

The nephrotic syndrome (NS) is a clinical entity of diverse etiology characterized by the proteinuria, hypoalvuninanemiam, hyperlipidemia, and edema. Glucocorticoid (GC) is the most important therapeutic agent in the treatment during clinical practice. However, the reactions of patients towards the steroids treatment are different. Some patients are sensitive to steroids, which means proteinuria becomes negative after 8 weeks of adequate steroid; while others aren't, which means that proteinuria still persists even after 12 weeks of steroid. Meanwhile, part of the NS patients are sensitive to GC initially, but due to infections or stress during the recession of GC, proteinuria become positive again and the patients start to develop steroid resistance. The mechanisms about the different reactions towards steroid treatment and steroid resistance are still unclear. But it is pretty clear that the rate of renal dysfunction of steroid resistant NS patient is far more than steroids sensitive NS patients. So our study aim to explore the mechanism of steroid resistance in NS.Objective: To explore the expression and the significance of GR,AP-1 and the inflammatory factors in steroid resistant NS patients.Meathod: The 45 patients of idiopathic nephrotic syndrome with the pathological pattern of minor glomerular abnormalities and slight mesangial proliferative glomerulonephritis were devided into 3 groups (steroid sensitive group, steroid resistant group and reoccurrent steroid resistant group) according to the response to the treatment with corticosteroids. ELISA was employed to detect the serum IL-1βand TNF-αlevels in NS patients. SP immunohistochemistry was employed to detect the expression of AP-1(c-jun and c-fos), which are the two major constituents of AP-1, GRα, and GRβin the three groups. Results: The serum IL-1βand TNF-αlevels in steroid sensitive group and recurrent steroid resistant group were higher than those in steroid resistant group( P<0.05), while there were no differences in serum IL-1βand TNF-αlevels between steroid resistant group and recurrent steroid resistant group( P>0.05). The expression of GRβ,c-jun,c-fos in steroid resistant group and recurrent steroid resistant group were higher than those in steroid sensitive group( P<0.05), while there were no differences in the expression of GRβ,c-jun,c-fos between steroid resistant group and recurrent steroid resistant group( P>0.05).The concentrations of GRαin steroid resistant group and recurrent steroid resistant group were lower than those in steroid sensitive group( P< 0.05).There were no difference in the concentrations of GRαbetween steroid resistant group and recurrent steroid resistant group( P>0.05).Conclusion: The high expression of AP-1(c-Jun,c-Fos),GRβand low expression of GRαwere found in the renal tissue of steroid resistant NS patients. The abnormal expression of GRαmay be the direct cause of steroid resistance. However, the exact mechanism of the abnormal expression of GRαand GRβneeds further study. The elevation of serum IL-1βand TNF-αlevels indicated the onset of steroid resistance.