Plasma exosomal miRNAs involved in endothelial injury in microscopic polyangiitis patients

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 MPAexo 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. K E Y W O R D Shigh-throughput sequencing, microRNA profile, plasma exosomes 6216 | WANG et Al.

Microscopic polyangiitis plasma-derived exosomal miR-1287-5p induces endothelial inflammatory injury and neutrophil adhesion by targeting CBL

“…Similar to other types of cells, vascular endothelial cells have the ability to produce and take up exosomes. Therefore, circulating exosomes may be captured by vascular endothelial cells throughout the body and cause cell injury, which may contribute to the various pathophysiologies of organs in the above-described diseases and MPA ( Gao et al, 2021 ; Roig-Carles et al, 2021 ; Wang et al, 2020 ). In the current study, we observed that exosomes isolated from the plasma of MPA patients and HC could be absorbed into HUVEC via endocytosis.…”

“…Exosomes are nanometre-sized microvesicles secreted by almost all mammalian cell types and range in size from 30 to 150 nm. Increasing evidence suggests that exosomes are abundant in biological fluids, including serum, and circulate with the fluids, facilitating communication between various cells and their microenvironment ( Prikryl et al, 2020 ; Surmiak et al, 2021 ; Wang et al, 2020 ). Exosomes deliver bioactive molecules, such as mRNA, microRNA (miRNA), long noncoding RNA, proteins, and lipids, from parental cells to recipient cells, playing an important role in many diseases, including cancer, AAV, and acute kidney injury ( Dong et al, 2019 ; Huang et al, 2020 ; Oh & Kwon, 2021 ).…”

“…Growing evidence suggests that the quality and quantity of circulating miRNA in AAV patients has changed compared with healthy individuals and is considered as reliable markers for diseases diagnosis and classification ( Skoglund et al, 2015 ). A recent study revealed significant correlations between exosomal miR-185-3p and miR-125a-3p and MPA disease activity ( Wang et al, 2020 ). In addition, exosomal miRNA derived from neutrophils preincubation with anti-PR3 IgG induces endothelial cells to release adhesion molecules and chemokines.…”

Knowledge Mapping of Exosomes in Autoimmune Diseases: A Bibliometric Analysis (2002–2021)

“…Qianjin Lu and Ming Zhao co-published 4 papers, two of which reviewed the research progress of exosomes in the pathogenesis, immune regulation and treatment of AIDs (53,58), and the two other articles pointed out the mechanism of serum exosomal miR-451a and miR-642-3p involved in the pathogenesis of SLE and SS (59,60). Wei Wei published 4 papers, three of which reviewed the pathogenesis of extracellular vesicles in vasculitis and lupus nephritis (LN) (61)(62)(63), and another article pointed out plasma exosomes participate in the inflammation process of microscopic polyangiitis (64). Besides, four papers authored by Jim Xiang mainly studied the immunomodulatory effects of exosomes derived from CD4 + T cells, CD8 + 25 + regulatory T cells (65-67) and dendritic cells (68) in mice.…”

MiR-126 Is an Independent Predictor of Long-Term All-Cause Mortality in Patients with Type 2 Diabetes Mellitus

“…More recently the association of platelet-related miRNAs was studied in ACS patients on DAPT and pathophysiological processes in the TDM population [ 16 , 19 , 20 , 21 , 22 , 23 ]. Among others, Let-7e and miR-125a-3p are molecules that have been formerly linked to inflammation, platelet reactivity, and mechanisms leading to diabetes; however, the impact of antiplatelet therapy on Let-7e and miR-125a-3p and their prognostic potential has not been studied so far [ 24 , 25 , 26 ]. Therefore, our aim was to analyze the impact of antiplatelet treatment on Let-7e and miR-125a-3p expressions and confirm the previous observations for miR-126 and miR-223 expressions, as well as investigate their usefulness as predictive biomarkers specifically in the T2DM cohort.…”