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

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.

• Authors: Mako Okabe, Shinya Takarada, Nariaki Miyao, Hideyuki Nakaoka, Keijiro Ibuki, Sayaka Ozawa, Kazuhiro Watanabe, Harue Tsuji, Ikuo Hashimoto, Kiyoshi Hatasaki, Shotaro Hayakawa, Yu Hamaguchi, Michiaki Hamada, Fukiko Ichida, Keiichi Hirono
• Journal: Pediatric research (Pediatr Res) Vol. 92 Issue 2 Pg. 378-387 (08 2022) ISSN: 1530-0447 [Electronic] United States
• PMID: 35292727 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.

Chemical References

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

Topics

• 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, metabolism)
• Tumor Necrosis Factor-alpha