Abstract: FR-PO054
MicroRNA-219c Dependent Mincle Is Critical for Maintaining Proinflammatory Phenotype of Macrophage in Renal Inflammation
Session Information
- AKI: Tubules, Metabolism, New Models
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Lv, Linli, Institute of Nephrology, Nanjing, China
- Li, Zuolin, Zhong Da Hospital, Southeast University,, Nanjing, JIANGSU , China
- Feng, Ye, Zhongda hospital, Southeast university, Nanjing, China
- Zhong, Xin, Institute of Nephrology, Zhongda Hospitial, Southeast University School of Medicine, Nanjing, China;, Nanjing, China
Background
Macrophages are a key inflammatory cell that plays a critical role in renal inflammation and fibrosis. Our previous study demonstrated that the pattern recognition receptor, Mincle is essential for maintaining inflammatory phenotypes of M1 macrophages in acute renal inflammation. However, the mechanism through which Mincle expression was regulated and its relation with different macrophage phenotypes remains largely unknown.
Methods
Unilateral urethral obstruction model of renal injury was established at day 1, 3, 7 to observe the dynamic change of Mincle expression and its relation with macrophage phenotype. For in vitro study, LPS and IL4 was used to induce M1, M2 polarization to explore Mincle expression in the process of phenotype switching. The regulatory effects of microRNA-219c in Mincle expression and kidney inflammation were also determined.
Results
During progression of renal inflammation in UUO model, Mincle+ macrophage significantly increased at day 1 while it decreased rapidly with theincreasing M2 macrophage infiltration. During macrophage phenotype switch, Mincle mRNA and protein was enhanced in LPS-primed M1 macrophage, while its expression decreased in M2 macrophage. Interestingly, Mincle overexpression induced proinflammatory phenotype polarization and also reversed the phenotype switching to M2 macrophage from either M0 or M1 macrophages. Bioinformatic analysis showed that Mincle was a potential target of microRNA-219c. Interestingly, microRNA-219c was reduced in injured kidney of UUO model when Minlce was upregulated at day1. Mincle protein was reduced in RAW264.7 with microRNA-219c mimic treatment. And the luciferase reporter gene assay confirmed that microRNA-219c was a novel regulator of Mincle expression. To explore the effect of microRNA-219c in renal inflammation, microRNA-219c was overexpressed in mice via lentivirus injection. Impressively, Mincle and inflammatory cytokines CCL2, IL6 mRNA was remarkably reduced in UUO kidney compared to empty vector group.
Conclusion
MicroRNA-219c was a novel regulator of Mincle which is critical for maintaining proinflammatory macrophage phenotype and contribute to renal inflammation. Targeting microRNA-219c-Mincle may represent as a novel therapy for macrophage-dependent kidney injury.
Funding
- Government Support - Non-U.S.