title: Differential expression of miR-145 in children with Kawasaki disease.
abstract: BACKGROUND
  Kawasaki disease is an acute, self-limited vasculitis of childhood that can result in structural damage to the coronary arteries. Previous studies have implicated the TGF-β pathway in disease pathogenesis and generation of myofibroblasts in the arterial wall. microRNAs are small non-coding RNAs that modulate gene expression at the post-transcriptional level and can be transported between cells in extracellular vesicles. To understand the role that microRNAs play in modifying gene expression in Kawasaki disease, we studied microRNAs from whole blood during the acute and convalescent stages of the illness.
  
  
  RESULTS
  RNA isolated from the matched whole blood of 12 patients with acute and convalescent Kawasaki disease were analyzed by sequencing of small RNA. This analysis revealed six microRNAs (miRs-143, -199b-5p, -618, -223, -145 and -145* (complementary strand)) whose levels were significantly elevated during the acute phase of Kawasaki disease. The result was validated using targeted qRT-PCR using an independent cohort (n = 16). miR-145, which plays a critical role in the differentiation of neutrophils and vascular smooth muscle cells, was expressed at high levels in blood samples from acute Kawasaki disease but not adenovirus-infected control patients (p = 0.005). miR-145 was also detected in small extracellular vesicles isolated from acute Kawasaki disease plasma samples. Pathway analysis of the predicted targets of the 6 differentially expressed microRNAs identified the TGF-β pathway as the top pathway regulated by microRNAs in Kawasaki disease.
  
  
  CONCLUSIONS
  Sequencing of small RNA species allowed discovery of microRNAs that may participate in Kawasaki disease pathogenesis. miR-145 may participate, along with other differentially expressed microRNAs, in regulating expression of genes in the TGF-β pathway during the acute illness. If the predicted target genes are confirmed, our findings suggest a model of Kawasaki disease pathogenesis whereby miR-145 modulates TGF-β signaling in the arterial wall.
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, California, USA. c1shimizu@ucsd.edu
authors.forename: Chisato
authors.initials: C
authors.lastname: Shimizu
authors.forename: Jihoon
authors.initials: J
authors.lastname: Kim
authors.forename: Petra
authors.initials: P
authors.lastname: Stepanowsky
authors.forename: Christine
authors.initials: C
authors.lastname: Trinh
authors.forename: Hubert D
authors.initials: HD
authors.lastname: Lau
authors.forename: Johnny C
authors.initials: JC
authors.lastname: Akers
authors.forename: Clark
authors.initials: C
authors.lastname: Chen
authors.forename: John T
authors.initials: JT
authors.lastname: Kanegaye
authors.forename: Adriana
authors.initials: A
authors.lastname: Tremoulet
authors.forename: Lucila
authors.initials: L
authors.lastname: Ohno-Machado
authors.forename: Jane C
authors.initials: JC
authors.lastname: Burns
mesh_terms: D001158:Arteries / Q000378:metabolism; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D007223:Infant; D035683:MicroRNAs / Q000097:blood*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009080:Mucocutaneous Lymph Node Syndrome / Q000097:blood / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D016212:Transforming Growth Factor beta