Abstract: SA-PO600
Upregulation of miR-98-5p Enhance the Level of Galactose-Deficient IgA1 Through Chemokines in IgA Nephropathy
Session Information
- Glomerular Diseases: Immunology, Inflammation - II
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Liu, Di, The Second Xiangya Hospital, Central South University, Changsha, China
- Liu, Hong, The Second Xiangya Hospital, Central South University, Changsha, China
Background
The increase of galactose-deficient IgA1 (Gd-IgA1) plays a crucial role in the pathogenesis of IgA nephropathy (IgAN). The aim of this study was to find the miRNA which could affect the pathogenesis of IgAN and reveal its regulation mechanism of Gd-IgA1 expression in peripheral blood.
Methods
The differentially expressed miRNAs in peripheral blood mononuclear cell (PBMC) between IgAN patients and healthy controls were screened by high-throughput sequencing. Confirm the results of the sequencing in a larger sample size. And explore the mechanism of the regulation of Gd-IgA1 caused by miRNA through transfecting miRNA mimic and related plasmid.
Results
High-throughput sequencing results showed that miR-98-5p is highly expressed in PBMC of IgA nephropathy patients compared with healthy controls, and the luciferase reporter gene system confirmed that miR-98-5p may target CCL3. miR-98-5p was increased and CCL3 was decreased in PBMC of IgAN patients were confirmed in a larger sample size, which was consistent with the sequencing results. It was confirmed by transfecting si-CCL3 that the decrease of CCL3 can affect the expression of interleukin-6 (IL-6) and C1GALT1.The overexpression of miR-98-5p in PBMC through transfecting the miR-98-5p mimic led to a reduction in CCL3 and C1GALT1 levels and an increase in IL-6 and Gd-IgA1 levels. But when co-transfected with the CCL3 plasmid, these changes in PBMC could be attenuated.
Conclusion
Hsa-miR-98-5p may be involved in the development of IgA nephropathy and is expected to become a biomarker and a new therapeutic target.
Figure 1. The changes in miR-98-5p expression of PBMCs in IgAN patients. Figure 2. miR-98-5p targets CCL3. Figure 3. CCL3 was down-regulated in IgAN patients. Figure 4. Th1/Th2/Th17 cytokines expression. Figure 5 CCL3 affects the expression of IL-6 and C1GALT1
Figure 6 PBMCs transfected with mimic-Cy3
Figure 7 miR-98-5p affects the expression of IL-6 and C1GALT1 and the level of Gd-IgA1 through CCL3