G0S2 regulates innate immunity in Kawasaki disease via lncRNA HSD11B1-AS1.
Journal
Pediatric research
ISSN: 1530-0447
Titre abrégé: Pediatr Res
Pays: United States
ID NLM: 0100714
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
19
03
2021
accepted:
02
02
2022
revised:
23
11
2021
pubmed:
17
3
2022
medline:
4
10
2022
entrez:
16
3
2022
Statut:
ppublish
Résumé
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. 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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 35292727
doi: 10.1038/s41390-022-01999-9
pii: 10.1038/s41390-022-01999-9
pmc: PMC8922062
doi:
Substances chimiques
Cell Cycle Proteins
0
G0S2 protein, human
0
RNA, Long Noncoding
0
Tumor Necrosis Factor-alpha
0
11-beta-Hydroxysteroid Dehydrogenase Type 1
EC 1.1.1.146
HSD11B1 protein, human
EC 1.1.1.146
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
378-387Informations de copyright
© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.
Références
Newburger, J. W. et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Circulation 110, 2747–2771 (2004).
pubmed: 15505111
doi: 10.1161/01.CIR.0000145143.19711.78
Kawasaki, T. Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children. Arerugi 16, 178–222 (1967).
pubmed: 6062087
McCrindle, B. W. et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation 135, e927–e999 (2017).
pubmed: 28356445
doi: 10.1161/CIR.0000000000000484
Dietz, S. M. et al. Dissecting Kawasaki disease: a state-of-the-art review. Eur. J. Pediatr. 176, 995–1009 (2017).
pubmed: 28656474
pmcid: 5511310
doi: 10.1007/s00431-017-2937-5
Verdoni, L. et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet 395, 1771–1778 (2020).
pubmed: 32410760
pmcid: 7220177
doi: 10.1016/S0140-6736(20)31103-X
Hara, T. et al. Kawasaki disease: a matter of innate immunity. Clin. Exp. Immunol. 186, 134–143 (2016).
pubmed: 27342882
pmcid: 5054572
doi: 10.1111/cei.12832
Hirata, S., Nakamura, Y. & Yanagawa, H. Incidence rate of recurrent Kawasaki disease and related risk factors: from the results of nationwide surveys of Kawasaki disease in Japan. Acta Paediatr. 90, 40–44 (2001).
pubmed: 11227331
doi: 10.1111/j.1651-2227.2001.tb00253.x
Ye, F. et al. Neutrophil-derived S100A12 is profoundly upregulated in the early stage of acute Kawasaki disease. Am. J. Cardiol. 94, 840–844 (2004).
pubmed: 15374807
doi: 10.1016/j.amjcard.2004.05.076
Ebihara, T. et al. Differential gene expression of S100 protein family in leukocytes from patients with Kawasaki disease. Eur. J. Pediatr. 164, 427–431 (2005).
pubmed: 15838637
doi: 10.1007/s00431-005-1664-5
Guttman, M. et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458, 223–227 (2009).
pubmed: 19182780
pmcid: 2754849
doi: 10.1038/nature07672
Zangrando, J. et al. Identification of candidate long non-coding RNAs in response to myocardial infarction. BMC Genomics 15, 460 (2014).
pubmed: 24917243
pmcid: 4070571
doi: 10.1186/1471-2164-15-460
Wang, X. et al. Early expressed circulating long noncoding RNA CHAST is associated with cardiac contractile function in patients with acute myocardial infarction. Int. J. Cardiol. 302, 15–20 (2020).
pubmed: 31924400
doi: 10.1016/j.ijcard.2019.12.058
Chen, S. et al. Comprehensive analysis and co-expression network of mRNAs and lncRNAs in pressure overload-induced heart failure. Front. Genet. 10, 1271 (2019).
pubmed: 31921308
pmcid: 6920101
doi: 10.3389/fgene.2019.01271
Ouyang, F. et al. Long non-coding RNA RNF7 promotes the cardiac fibrosis in rat model via miR-543/THBS1 axis and TGFβ1 activation. Aging 12, 996–1010 (2020).
pubmed: 31913855
pmcid: 6977683
doi: 10.18632/aging.102463
Ayusawa, M. et al. Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition). Pediatr. Int. 47, 232–234 (2005).
pubmed: 15771703
doi: 10.1111/j.1442-200x.2005.02033.x
Li, H. & Durbin, R. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 26, 589–595 (2010).
pubmed: 20080505
pmcid: 2828108
doi: 10.1093/bioinformatics/btp698
Kim, D., Langmead, B. & Salzberg, S. L. HISAT: a fast spliced aligner with low memory requirements. Nat. Methods 12, 357–360 (2015).
pubmed: 25751142
pmcid: 4655817
doi: 10.1038/nmeth.3317
Ohmiya, H. et al. RECLU: a pipeline to discover reproducible transcriptional start sites and their alternative regulation using capped analysis of gene expression (CAGE). BMC Genomics 15, 269 (2014).
pubmed: 24779366
pmcid: 4029093
doi: 10.1186/1471-2164-15-269
Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140 (2010).
pubmed: 19910308
doi: 10.1093/bioinformatics/btp616
Young, M. D., Wakefield, M. J., Smyth, G. K. & Oshlack, A. Gene ontology analysis for RNA-seq: accounting for selection bias. Genome Biol. 11, R14 (2010).
pubmed: 20132535
pmcid: 2872874
doi: 10.1186/gb-2010-11-2-r14
Russell, L. & Forsdyke, D. R. A human putative lymphocyte G0/G1 switch gene containing a CpG-rich island encodes a small basic protein with the potential to be phosphorylated. DNA Cell Biol. 10, 581–591 (1991).
pubmed: 1930693
doi: 10.1089/dna.1991.10.581
Kobayashi, S. et al. Expression profiling of PBMC-based diagnostic gene markers isolated from vasculitis patients. DNA Res. 15, 253–265 (2008).
pubmed: 18562305
pmcid: 2575881
doi: 10.1093/dnares/dsn014
Jakobsson, P. J. Pain: how macrophages mediate inflammatory pain via ATP signaling. Nat. Rev. Rheumatol. 6, 679–681 (2010).
pubmed: 21119716
doi: 10.1038/nrrheum.2010.175
Kioka, H. et al. Evaluation of intramitochondrial ATP levels identifies G0/G1 switch gene 2 as a positive regulator of oxidative phosphorylation. Proc. Natl Acad. Sci. USA 111, 273–278 (2014).
pubmed: 24344269
doi: 10.1073/pnas.1318547111
Furukawa, S., Matsubara, T. & Yabuta, K. Mononuclear cell subsets and coronary artery lesions in Kawasaki disease. Arch. Dis. Child. 67, 706–708 (1992).
pubmed: 1378258
pmcid: 1793803
doi: 10.1136/adc.67.6.706
Luo, Y. et al. Up-regulation of miR-27a promotes monocyte-mediated inflammatory responses in Kawasaki disease by inhibiting function of B10 cells. J. Leukoc. Biol. 107, 133–144 (2020).
pubmed: 31583766
doi: 10.1002/JLB.5A0919-075RR
Takahashi, K., Oharaseki, T., Yokouchi, Y., Hiruta, N. & Naoe, S. Kawasaki disease as a systemic vasculitis in childhood. Ann. Vasc. Dis. 3, 173–181 (2010).
pubmed: 23555407
pmcid: 3595783
doi: 10.3400/avd.sasvp01003
Sato, N., Sagawa, K., Sasaguri, Y., Inoue, O. & Kato, H. Immunopathology and cytokine detection in the skin lesions of patients with Kawasaki disease. J. Pediatr. 122, 198–203 (1993).
pubmed: 8094096
doi: 10.1016/S0022-3476(06)80113-7
Nishio, H. et al. Nod1 ligands induce site-specific vascular inflammation. Arterioscler. Thromb. Vasc. Biol. 31, 1093–1099 (2011).
pubmed: 21330608
doi: 10.1161/ATVBAHA.110.216325
Motomura, Y. et al. Identification of pathogenic cardiac CD11c+ macrophages in Nod1-mediated acute coronary arteritis. Arterioscler. Thromb. Vasc. Biol. 35, 1423–1433 (2015).
pubmed: 25838430
doi: 10.1161/ATVBAHA.114.304846
Lin, I. C. et al. Augmented TLR2 expression on monocytes in both human Kawasaki disease and a mouse model of coronary arteritis. PLoS ONE 7, e38635 (2012).
pubmed: 22737215
pmcid: 3380902
doi: 10.1371/journal.pone.0038635
Armaroli, G. et al. Monocyte-derived interleukin-1β as the driver of S100A12-induced sterile inflammatory activation of human coronary artery endothelial cells: implications for the pathogenesis of Kawasaki disease. Arthritis Rheumatol. 71, 792–804 (2019).
pubmed: 30447136
doi: 10.1002/art.40784
Huang, Y. H. et al. Identifying genetic hypomethylation and upregulation of toll-like receptors in Kawasaki disease. Oncotarget 8, 11249–11258 (2017).
pubmed: 28061462
pmcid: 5355262
doi: 10.18632/oncotarget.14497
Yin, W. et al. Expression of nuclear factor -κBp65 in mononuclear cells in Kawasaki disease and its relation to coronary artery lesions. Indian J. Pediatr. 78, 1378–1382 (2011).
pubmed: 21688043
doi: 10.1007/s12098-011-0478-x
Carrieri, C. et al. Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. Nature 491, 454–457 (2012).
pubmed: 23064229
doi: 10.1038/nature11508
Ko, T. M. et al. Genome-wide transcriptome analysis to further understand neutrophil activation and lncRNA transcript profiles in Kawasaki disease. Sci. Rep. 9, 328 (2019).
pubmed: 30674924
pmcid: 6344526
doi: 10.1038/s41598-018-36520-y
Li, X., Zhou, J. & Huang, K. Inhibition of the lncRNA Mirt1 attenuates acute myocardial infarction by suppressing NF-κB activation. Cell. Physiol. Biochem. 42, 1153–1164 (2017).
pubmed: 28668956
doi: 10.1159/000478870
Zhao, J. & Chen, D. Kawasaki disease: SOCS2-AS1/miR-324-5p/CUEDC2 axis regulates the progression of human umbilical vein endothelial cells. Pediatr. Res. 20, 1–8 (2020).
Arner, E. et al. Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells. Science 347, 1010–1014 (2015).
pubmed: 25678556
pmcid: 4681433
doi: 10.1126/science.1259418
Kawaji, H. et al. Comparison of CAGE and RNA-seq transcriptome profiling using clonally amplified and single-molecule next-generation sequencing. Genome Res. 24, 708–717 (2014).
pubmed: 24676093
pmcid: 3975069
doi: 10.1101/gr.156232.113
Liu, S. et al. Annotation and cluster analysis of spatiotemporal- and sex-related lncRNA expression in rhesus macaque brain. Genome Res. 27, 1608–1620 (2017).
pubmed: 28687705
pmcid: 5580719
doi: 10.1101/gr.217463.116
O’Grady, T. et al. Genome-wide transcript structure resolution reveals abundant alternate isoform usage from murine gammaherpesvirus 68. Cell Rep. 27, 3988.e5–4002.e5 (2019).
doi: 10.1016/j.celrep.2019.05.086