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

Abstract

Objective: The 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).

Methods: Peripheral 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.

Results: Tregs 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.

Conclusion: MiR-133a and miR-133b inhibited Treg differentiation in IgA nephropathy through targeting FOXP3.

Keywords: FOXP3; IgA nephropathy; Treg differentiation; miR-133a/133b.