Abstract: FR-PO227

MicroRNA-21 Participates in IgA Nephropathy by Driving T Helper Cell Polarization

Session Information

Category: Cell Biology

  • 202 Apoptosis, Proliferation, Autophagy, Cell Senescence, Cell Transformation

Authors

  • Sijun, Meng, Peking university first hospital, Beijing, China
  • Zhang, Hong, Peking University First Hospital, Beijing, China
  • Zhu, Li, Renal Division, Peking University First Hospital, Beijing, China
Background

Previous studies revealed abnormal lymphocytes subsets in IgA nephropathy (IgAN). Recently, emerging studies indicate that miR-21 alters the balance of T helper cells differentiation and function. Here we explored the participation of miR-21 in IgAN, especially focused on T helper cell polarization.

Methods

Totally, 38 IgAN patients and 35 healthy controls (HC) were enrolled. Firstly, miRNAs and mRNA profiles in PBMC were determined by next-generation sequencing and gene expression array. Then, above identified miRNA were tested in both CD19+ B cells and CD3+ T cells. After the confirmation of differently expressed miRNA, expression of the miRNA target genes were further verified using real-time PCR. Meanwhile, T helper cells subgroups (Th1, Th2 and Th17), as well as plasma IgA1 and galactose deficient IgA1 (Gd-IgA1) levels were detected by FC and ELISA.

Results

MiR-21 showed highest level among 22 differently expressed miRNAs between IgANs and HCs. Through combined analysis of miRNA and mRNA profile data, SPRY1, SPRY2, FASLG were chosen as target genes for miR-21, for their negative correlation with miR-21 and bearing target sequence of miR-21. Next, we found that miR-21 levels in IgAN were only higher in CD3+ T cells (9.3±7.3 vs 4.0±3.4, p=0.02), but not CD19+ B cells. Accordingly, the mRNA levels of SPRY1, SPRY2, FASLG from CD3+ T cells were lower in IgAN than in HC (1.5±1. 3 vs 2.9±1.6, p<0.01; 1.2±1.2 vs 2.5±2.2, p<0.01; 0.9±0.6 vs 1.6±1.1, p<0.01). And miR-21 showed negative correlation with SPRY1 (r=-0.37, p<0. 01), while similar trend of correlation were observed to SPRY2 (r=-0.33, p=0.05) and FASLG (r=-0.31, p=0.07). FC analysis revealed elevated Th17 cells in IgAN than in HC (15.0±4.5 vs 12.6±1.8, p=0.04). Moreover, negative correlations were found between Th17 cells and SPRY1 (r=-0.33, p=0.04), SPRY2 (r=-0.36, p=0.03), FASLG;(r=-0.47, p<0.01). And in our recruited IgAN, the proportion of Th17 cells only showed a trend of positive correlation with plasma IgA1 (r=0.3, p=0.06), but not Gd-IgA1.

Conclusion

Our results showed higher miR-21 levels in IgAN, which inhibited the expression of SPRY1, SPRY2, FASLG, and thereby accelerated Th17 polarization.

Funding

  • Government Support - Non-U.S.