Abstract:

AIM: To determine the expression of glucocorticoid (GC) receptor GRα/GRβ and splicing factor SRp40 in peripheral blood mono-nuclear cells (PBMC) of nephrotic syndrome (NS) patients so as to investigate the regulating effect of splicing factor on GC and differential expression of GC receptor on GC therapy. METHODS: Twenty healthy volunteers and 46 NS patients were included. The NS patients were divided into GC-sensitive (n=24) and GC-resistant group (n=22) according to the response to GC therapy. Quantitative Real-time PCR was performed to investigate the mRNA expression of GRα/GRβ and SRp40 in healthy volunteers and NS patients before and after glucocorticoid treatment. The expression level of GRα/GRβ and SRp40 mRNA were compared between groups and analyzed to assess the relevance of GC receptor and slicing factor and their effect on clinical outcomes. RESULTS: The expression of GRα and GRβ mRNA were detected both in control and NS patients with the GRα as the domination sub-type, and no significant difference was observed between GC-sensitive and GC-resistant group. While the expression of SRp40 mRNA on PBMC in GC-resistant group was significantly higher than that in GC-sensitive group and in health control (P=0.035). The expression level of GR  in GC-resistant group was significantly increased after GC treatment （P<0.001）, but no significant difference of the GRα mRNA expression was observed between NS groups.  And the expression of GRβ mRNA level was found positively associated with SRp40 level through linear regression method. CONCLUSION:The over expression of SRp40 can induce the over expression of GRβ mRNA through modulating alternative splicing, which may be a risk factor in the resistance of GC in NS patients. And levels of GRβ and SRp40 mRNA may be predictors for GC resistance in NS patients.

Key words: nephrotic syndrome, glucocorticoid resistance, glucocorticoid receptor α/β, splicing factor SRp40