Background: Kawasaki 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.
Methods: To examine this hypothesis, we conducted a meta-analysis, miRNA mimic transfection, in vitro cell model and microarray assays.
Results: We 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).
Conclusion: Therefore, our study suggested that miR-182-5p enhanced in vitro leukocyte infiltration by activating the leukocyte transendothelial migration pathway in CAL formation in KD.
Keywords: Kawasaki disease; coronary artery lesion; leukocyte transendothelial migration; miR-182-5p; neutrophil infiltration.
© 2019 Kaohsiung Veterans General Hospital / Kaohsiung Chang Gung Memorial Hospital. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.