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

• Published in: Pediatric research Vol. 92; no. 2; pp. 378 - 387
• Main Authors: Okabe, Mako, Takarada, Shinya, Miyao, Nariaki, Nakaoka, Hideyuki, Ibuki, Keijiro, Ozawa, Sayaka, Watanabe, Kazuhiro, Tsuji, Harue, Hashimoto, Ikuo, Hatasaki, Kiyoshi, Hayakawa, Shotaro, Hamaguchi, Yu, Hamada, Michiaki, Ichida, Fukiko, Hirono, Keiichi
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2022; Nature Publishing Group
• Subjects: Basic Science; Basic Science Article; Gene expression; Immunity (Disease); Inflammation; Kawasaki disease; Medicine; Medicine & Public Health; Pediatric Surgery; Pediatrics
• ISSN: 0031-3998; 1530-0447; 1530-0447
• DOI: 10.1038/s41390-022-01999-9

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.