TY - JOUR
T1 - G0S2 regulates innate immunity in Kawasaki disease via lncRNA HSD11B1-AS1
AU - Okabe, Mako
AU - Takarada, Shinya
AU - Miyao, Nariaki
AU - Nakaoka, Hideyuki
AU - Ibuki, Keijiro
AU - Ozawa, Sayaka
AU - Watanabe, Kazuhiro
AU - Tsuji, Harue
AU - Hashimoto, Ikuo
AU - Hatasaki, Kiyoshi
AU - Hayakawa, Shotaro
AU - Hamaguchi, Yu
AU - Hamada, Michiaki
AU - Ichida, Fukiko
AU - Hirono, Keiichi
N1 - Funding Information:
We are grateful to Professor Yuichi Adachi. We thank our colleagues and collaborating hospitals for always supporting us: Hitoshi Moriuchi, Haruna Hirai, Eriko Masuda, Miho Arai, Syokei Murakami, Shintaro Terashita, Yu Saito, Haruka Ushio, Taisuke Kato, Nao Sakata, Asami Takasaki, Osamu Higuchi, Tomoko Sakuma, Yoshie Okabe, Junko Yamaoto, Tatsuya Fuchizawa, Keiichiro Uese, Shinichi Tsubata, Itaru Yamaguchi, Yujiro Takegami, Ichiro Takasaki, Kesuke Okabe, and Koshi Kinoshita.
Funding Information:
This study was supported by Grant-in-Aid for Scientific Research 00831041 (to M.O.) from the Ministry of Education, Culture, Sports, Science and Technology, Grant-in-Aid from Japanese Kawasaki Disease Research Center (to M.O.), and a grant for Kawasaki Disease Research from Japan Blood Products Organization (to M.O.).
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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.
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U2 - 10.1038/s41390-022-01999-9
DO - 10.1038/s41390-022-01999-9
M3 - Article
C2 - 35292727
AN - SCOPUS:85126287397
SN - 0031-3998
VL - 92
SP - 378
EP - 387
JO - Pediatric Research
JF - Pediatric Research
IS - 2
ER -