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
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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.
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We demonstrated that G0S2 and its antisense HSD11B1-AS1 were associated with inflammation of innate immunity in KD.
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lncRNA may be a novel key target for the diagnosis of patients with KD.
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Acknowledgements
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
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.).
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M.O. collected all data. M.O., K. Hirono, S.H., Y.H, M.H., and F.I. designed the study. S.T., N.M., H.N., K.I., S.O., K.W., I.H., H.T., and K. Hatasaki provided the specimens. M.O., S.H., Y.H., M.H., F.I., and K. Hirono analyzed the data. M.O., F.I., and K. Hirono wrote the manuscript. All authors reviewed the manuscript.
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This study was approved by the ethics committee of the University of Toyama and conducted according to the Declaration of Helsinki. Patients and controls were enrolled after obtaining informed consent from their parents or legal guardians.
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Okabe, M., Takarada, S., Miyao, N. et al. G0S2 regulates innate immunity in Kawasaki disease via lncRNA HSD11B1-AS1. Pediatr Res 92, 378–387 (2022). https://doi.org/10.1038/s41390-022-01999-9
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DOI: https://doi.org/10.1038/s41390-022-01999-9
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