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Published on: October 13, 2023
MiR-133a/133b inhibits Treg differentiation in IgA nephropathy through targeting FOXP3
Ling-Wei Jin1, Han-Yang Ye1, Xiao-Yan Xu1
1Department of Nephrology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
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.
Insights
MicroRNAs miR-133a and miR-133b inhibit regulatory T cell (Treg) differentiation in IgA nephropathy by targeting FOXP3. Lower Treg percentages in IgA nephropathy patients correlate with higher miR-133a and miR-133b levels.
Area of Science:
- Immunology
- Molecular Biology
- Nephrology
Background:
- IgA nephropathy (IgAN) is a kidney disease characterized by immune dysregulation.
- Regulatory T cells (Tregs) play a crucial role in maintaining immune tolerance.
- The specific molecular mechanisms regulating Treg differentiation in IgAN are not fully understood.
Purpose of the Study:
- To investigate the role of miR-133a and miR-133b in Treg differentiation in IgA nephropathy.
- To determine if miR-133a and miR-133b target forkhead box P3 (FOXP3) to influence Treg differentiation.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) were collected from IgAN patients and healthy controls.
- Flow cytometry was used to quantify Treg percentages (CD4+CD25+FOXP3+).
- Real-time PCR and western blotting assessed the expression of miR-133a, miR-133b, and FOXP3.
Main Results:
- IgAN patients exhibited significantly lower Treg percentages compared to healthy controls.
- miR-133a and miR-133b expression levels were significantly higher in IgAN patients.
- Treg percentage was negatively correlated with miR-133a and miR-133b levels, and FOXP3 expression was also reduced.
Conclusions:
- miR-133a and miR-133b inhibit Treg differentiation in IgA nephropathy.
- These microRNAs target FOXP3, a key transcription factor for Treg function.
- The findings suggest a novel mechanism contributing to immune dysregulation in IgAN.
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