miR-10b-5p drives Kawasaki-like vasculitis in mice; serum CXCL8 proposed as an early marker in children
Authors report that blocking miR-10b-5p reduced aortic root inflammation in mouse models, and serum CXCL8 was higher in children with Kawasaki disease at their first emergency department visit.
A preprint on bioRxiv (Cold Spring Harbor Laboratory) reports that the circulating microRNA miR-10b-5p promotes vasculitis in mouse models of Kawasaki disease. The same work found elevated serum CXCL8 in patients at first presentation to the emergency department nature.com
bioRxiv (Cold Spring Harbor Laboratory)nature.comOpen source ↗. Kawasaki disease is an acute systemic vasculitis of unknown cause and the leading cause of acquired heart disease in children. Coronary artery aneurysm is its most serious complication, and no specific biomarker exists for early diagnosis.
From patient samples to mouse models
The authors performed whole microRNA sequencing on buffy coat samples from Kawasaki disease patients and febrile controls presenting to the emergency department. Forty miRNAs were upregulated in patients, and fourteen were prioritized for further analysis. miR-10b-5p was consistently elevated in two independent mouse models of Kawasaki-like vasculitis. One used Lactobacillus casei cell wall extract (n=12–20) and the other a water-soluble fraction of Candida albicans (n=12). In the first model, inhibiting miR-10b-5p with an antagomir attenuated aortic root inflammation.
Mechanism in coronary endothelial cells
In human coronary artery endothelial cells, miR-10b-5p suppressed its direct targets MKI67 and CBX5. This shifted cells from proliferative and metabolic programs toward a pro-inflammatory phenotype, and bulk RNA-seq analysis supported cell-cycle arrest and altered chromatin remodeling. ATAC-seq showed increased chromatin accessibility at the CXCL8 and MMP10 promoters. Motif analysis pointed to the transcription factor CEBPA as the key activator, and CEBPA knockdown abolished the miR-10b-5p–induced rise in CXCL8 and MMP10.
Serum CXCL8 as a candidate marker
Measured by ELISA, serum CXCL8 was markedly higher in Kawasaki disease patients than in febrile controls at the first emergency department visit, before a definitive diagnosis. It declined significantly at the 8-week follow-up nature.com
bioRxiv (Cold Spring Harbor Laboratory)nature.comOpen source ↗. The authors describe a miR-10b-5p–MKI67/CBX5–CEBPA–CXCL8 axis as a driver of endothelial reprogramming and neutrophil-recruiting inflammation. They propose serum CXCL8 as a candidate early diagnostic biomarker. The mechanistic findings come from cell cultures and mouse models, and the marker has so far been described only as a candidate.
