Plasma exosomal miRNAs involved in endothelial injury in microscopic polyangiitis patients
Yang Wang1, Yingyu Bai1, Yixin Liu2
1Department of Clinical Immunology, School of Medical Laboratory, Tianjin Medical University, Tianjin, China.
Abstract:
Microscopic polyangiitis (MPA) is a systemic autoimmune disease that primarily affects the small and medium blood vessels. Endothelial injury is one of the pathological hallmarks of MPA. However, the pathogenesis for this has not yet been fully elucidated. Exosomal microRNAs (miRNAs) have recently emerged as a new molecular pattern involved in the endothelial injury in other diseases. Hence, we speculated that MPA plasma-derived exosomes (MPA-exo) could induce the endothelial injury, which was likely to be aroused by the dysregulated exosomal miRNAs in MPA. In the present study, plasma-derived exosomes were isolated and identified. MPA-exo could be internalized by human renal glomerular endothelial cells (HRGECs) in vitro and induced HRGECs injury. Subsequently, a series of differentially expressed miRNAs in MPA-exo were identified by high-throughput sequencing analysis. Further bioinformatics analysis for the target genes of these differentially expressed miRNAs showed a potential mechanism for their possible role in MPA endothelial injury. Notably, we revealed a considerable correlation between miR-185-3p, miR-125a-3p, and clinical parameters. In conclusion, the current study revealed that differentially expressed miRNAs in MPA-exo are associated with the endothelial injury. Our results suggested that these miRNAs and their target genes might be involved in the inflammation process of MPA.
Insights
Microscopic polyangiitis (MPA) plasma exosomes induce kidney endothelial cell injury, driven by altered microRNAs. These exosomal microRNAs and their targets may play a role in MPA pathogenesis.
Area of Science:
- Immunology
- Molecular Biology
- Pathology
Background:
- Microscopic polyangiitis (MPA) is an autoimmune disease causing small and medium blood vessel inflammation.
- Endothelial injury is a key feature of MPA, but its underlying mechanisms remain unclear.
- Exosomal microRNAs (miRNAs) are implicated in endothelial injury in other conditions.
Purpose of the Study:
- To investigate if plasma-derived exosomes from MPA patients induce endothelial injury.
- To identify differentially expressed miRNAs within these exosomes.
- To explore the potential role of these exosomal miRNAs in MPA pathogenesis.
Main Methods:
- Isolation and characterization of plasma-derived exosomes from MPA patients (MPA-exo).
- In vitro assessment of MPA-exo internalization and injury induction in human renal glomerular endothelial cells (HRGECs).
- High-throughput sequencing and bioinformatics analysis to identify differentially expressed miRNAs and their targets in MPA-exo.
Main Results:
- MPA-exo were successfully isolated and confirmed to be internalized by HRGECs, causing cellular injury.
- A distinct profile of differentially expressed miRNAs was identified in MPA-exo compared to controls.
- Bioinformatics analysis suggested potential mechanisms linking these miRNAs and their targets to MPA-related endothelial dysfunction.
- Specific miRNAs (miR-185-3p, miR-125a-3p) showed correlation with clinical parameters.
Conclusions:
- Dysregulated exosomal miRNAs in MPA plasma are associated with endothelial injury.
- These miRNAs and their downstream targets may contribute to the inflammatory processes in MPA.
- Exosomal miRNAs represent a potential avenue for understanding and possibly targeting MPA pathogenesis.
