The upregulation of miR-98-5p affects the glycosylation of IgA1 through cytokines in IgA nephropathy

Di Liu; Ming Xia; Yexin Liu; Xia Tan; Liyu He; Yu Liu; Guochun Chen; Hong Liu

doi:10.1016/j.intimp.2020.106362

The upregulation of miR-98-5p affects the glycosylation of IgA1 through cytokines in IgA nephropathy

Int Immunopharmacol. 2020 Feb 29:82:106362. doi: 10.1016/j.intimp.2020.106362. Online ahead of print.

Authors

Di Liu¹, Ming Xia¹, Yexin Liu¹, Xia Tan¹, Liyu He¹, Yu Liu¹, Guochun Chen¹, Hong Liu²

Affiliations

¹ Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, No. 139 Renmin Middle Road, Changsha 410011, Hunan, China.
² Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, No. 139 Renmin Middle Road, Changsha 410011, Hunan, China. Electronic address: liuhong618@csu.edu.cn.

PMID: 32126510
DOI: 10.1016/j.intimp.2020.106362

Abstract

Objective: Increases in galactose-deficient IgA1 (Gd-IgA1) play a crucial role in the pathogenesis of IgA nephropathy (IgAN), and several recent experiments have shown that microRNAs (miRNAs) are involved in regulating the development and physiological function of the kidney. The aims of this study were to identify miRNAs that can affect the pathogenesis of IgAN and reveal the underlying regulatory mechanism of IgA1 glycosylation in peripheral blood.

Methods: The differentially expressed miRNAs in peripheral blood mononuclear cells (PBMCs) between IgAN patients and healthy controls were screened by high-throughput sequencing, and the targets of these miRNAs were predicted and verified by dual-luciferase reporter assays. We also explored the miRNA regulation of Gd-IgA1 through the transfection of miRNA mimics and related plasmids.

Results: The high-throughput sequencing results showed that miR-98-5p was more highly expressed in the PBMCs of IgAN patients compared with healthy controls, and the luciferase reporter gene system confirmed that miR-98-5p might target chemokine ligand 3 (CCL3). The transfection of si-CCL3 confirmed that a decrease in CCL3 can affect the expression of interleukin-6 (IL-6) and C1GALT1. The overexpression of miR-98-5p in PBMCs through the transfection of miR-98-5p mimic reduced the CCL3 and C1GALT1 levels and increased the IL-6 levels, and these changes in PBMCs were attenuated by cotransfection with the CCL3 plasmid.

Conclusion: The results showed that in PBMCs, miR-98-5p can target CCL3 to decrease its expression and thereby increase the IL-6 levels, and the resulting increase in IL-6 can decrease C1GALT1 expression. Therefore, miR-98-5p might be involved in the development of IgAN.

Keywords: Chemokine ligand 3; Galactose-deficient IgA1; IgA nephropathy; Interleukin 6; miR-98-5p.