MiR‐182‐5p enhances in vitro neutrophil infiltration in Kawasaki disease

Abstract

BackgroundKawasaki disease (KD) patients could develop coronary artery lesion (CAL) which threatens children's life. A previous study identified KD biomarker miRNAs that could discriminate KD patients from febrile non‐KD patients. We wonder whether these KD prediction biomarkers could be further applied to predict CAL formation in KD patients.MethodsTo examine this hypothesis, we conducted a meta‐analysis, miRNA mimic transfection, in vitro cell model and microarray assays.ResultsWe first showed that miR‐182‐5p and miR‐183‐5p kept higher levels in the KD patients with CAL than those without CAL (p < .05). Further machine learning alignment confirmed that CAL formation could be predicted, with an auROC value of 0.86. We further treated neutrophil cells with miR‐182‐5p mimic, followed by in vitro transendotherial migration assay. As a result, miR‐182‐5p overexpression significantly (p < .05) enhanced neutrophil cells to infiltrate the endothelial layer composed of human coronary artery endothelium cells. Further microarray assay and pathway enrichment analysis showed that the genes activated with miR‐182‐5p overexpression were significantly enriched in the leukocyte transendothelial migration pathway (kegg_pathway_194, p < .05).ConclusionTherefore, our study suggested that miR‐182‐5p enhanced in vitro leukocyte infiltration by activating the leukocyte transendothelial migration pathway in CAL formation in KD.

Serum proteins may facilitate the identification of Kawasaki disease and promote in vitro neutrophil infiltration

“…We further used the concentrations of the six protein biomarkers to derive KD prediction models with one type of machine learning algorithm, support vector machine (SVM, lib-svm version 3.22) to conduct the binary classification jobs as previous studies 21 , 28 . In summary, we first conducted tenfold cross validation to derive the best parameters, gamma = 0.03125 and cost = 4.…”

“…The subsequent ELISA validation identified KD biomarkers which enabled us to develop a high-performance KD prediction model. By using an in vitro cell model applied in a previous study 21 , we also investigated the pathogenic roles of S100A12 in KD. We concluded that S100A12 treatment promoted neutrophil cell infiltration through the endothelial layer in vitro.…”

Comparable bidirectional neutrophil immune dysregulation between Kawasaki disease and severe COVID-19

“…More importantly, both neutrophil migration and transformation were associated with shock syndrome, a refractory response to IVIG and coronary artery lesions (CAL) in KD ( 34 – 36 ). Neutrophil activation has been reported to be enhanced with a marked increase in ROS, which contributes to the excessive formation of neutrophil extracellular traps (NETs), which has been suggested as being involved in the pathogenesis of KD ( 31 , 37 – 39 ), as well as the severity of acute respiratory syndrome caused by SARS-CoV-2 and severe COVID-19 patients who have cardiovascular injuries ( 40 – 42 ). One recent study profiled whole blood transcriptomes of COVID-19 patients and found that neutrophil activation signatures were predominantly enriched in the severe COVID-19 group, which was confirmed via granulocyte sample validation of an independent cohort of COVID-19 patients ( 43 ).…”

MicroRNAs in Kawasaki disease: An update on diagnosis, therapy and monitoring

“…found that the expression of miR-182-5p increased in the serum of patients with CALs compared to those without CALs. Through pathway enrichment and further experiments on human umbilical vein endothelial cells (HUVECs) and neutrophils, they concluded that miR-182-5p could enhance neutrophil infiltration to induce the CAL formation via activating the leukocyte trans-endothelial migration pathway ( 75 ). Besides, a recent pathway enrichment analysis revealed that the target genes of miR-223-3p are mainly distributed on the T cell receptor and B cell receptor pathways, which are highly relative to immune function ( 76 ).…”