G0S2 regulates innate immunity in Kawasaki disease via lncRNA HSD11B1-AS1

Pediatr Res. 2022 Aug;92(2):378-387. doi: 10.1038/s41390-022-01999-9. Epub 2022 Mar 15.

Abstract

Background: Kawasaki disease (KD) is a systemic vasculitis that is currently the most common cause of acquired heart disease in children. However, its etiology remains unknown. Long non-coding RNAs (lncRNAs) contribute to the pathophysiology of various diseases. Few studies have reported the role of lncRNAs in KD inflammation; thus, we investigated the role of lncRNA in KD inflammation.

Methods: A total of 50 patients with KD (median age, 19 months; 29 males and 21 females) were enrolled. We conducted cap analysis gene expression sequencing to determine differentially expressed genes in monocytes of the peripheral blood of the subjects.

Results: About 21 candidate lncRNA transcripts were identified. The analyses of transcriptome and gene ontology revealed that the immune system was involved in KD. Among these genes, G0/G1 switch gene 2 (G0S2) and its antisense lncRNA, HSD11B1-AS1, were upregulated during the acute phase of KD (P < 0.0001 and <0.0001, respectively). Moreover, G0S2 increased when lipopolysaccharides induced inflammation in THP-1 monocytes, and silencing of G0S2 suppressed the expression of HSD11B1-AS1 and tumor necrosis factor-α.

Conclusions: This study uncovered the crucial role of lncRNAs in innate immunity in acute KD. LncRNA may be a novel target for the diagnosis of KD.

Impact: This study revealed the whole aspect of the gene expression profile of monocytes of patients with Kawasaki disease (KD) using cap analysis gene expression sequencing and identified KD-specific molecules: G0/G1 switch gene 2 (G0S2) and long non-coding RNA (lncRNA) HSD11B1-AS1. We demonstrated that G0S2 and its antisense HSD11B1-AS1 were associated with inflammation of innate immunity in KD. lncRNA may be a novel key target for the diagnosis of patients with KD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • Cell Cycle Proteins
  • Child
  • Female
  • Humans
  • Immunity, Innate
  • Infant
  • Inflammation
  • Male
  • Mucocutaneous Lymph Node Syndrome* / genetics
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Tumor Necrosis Factor-alpha

Substances

  • Cell Cycle Proteins
  • G0S2 protein, human
  • RNA, Long Noncoding
  • Tumor Necrosis Factor-alpha
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • HSD11B1 protein, human