MiR-133a/133b inhibits Treg differentiation in IgA nephropathy through targeting FOXP3

Abstract

ObjectiveThe aim of this study was to investigate the effect of miR-133a and miR-133b on regulatory T cell (Treg) differentiation in IgA nephropathy (IgAN) through targeting forkhead box P3 (FOXP3). MethodsPeripheral blood mononuclear cells (PBMCs) were isolated from IgAN patients (n = 20) and healthy controls (n = 20). Percentage of Tregs defined as CD4 + CD25 + FOXP3 + T cells were determined by flow cytometry. The mRNA expression levels of miR-133a, miR-133b and FOXP3 were measured by real-time PCR. FOXP3 protein level was analyzed by western blotting. ResultsTregs percentage in PBMCs of IgAN patients was significantly lower than that of healthy controls, whereas the expression levels of miR-133a and miR-133b in IgAN patients were dramatically higher than that in the control group. Treg percentage was negatively correlated with miR-133a and miR-133b expressions. Meanwhile, miR-133a and miR-133b modulated FOXP3 expression by detecting of its gene 3′-untranslated region. MiR-133a or miR-133b overexpression significantly decreased the % Tregs (CD4 + CD25 + FOXP3+) of the total CD4 + T cells while miR-133a or miR-133b knockdown led to an opposite effect. Moreover, FOXP3 levels in IgAN patients was significantly lower than that in the control group and was negatively correlated with miR-133a and miR-133b expression. ConclusionMiR-133a and miR-133b inhibited Treg differentiation in IgA nephropathy through targeting FOXP3.