Genetic variants of ADAM17 are implicated in the pathological process of Kawasaki disease and secondary coronary artery lesions via the TGF-β/SMAD3 signaling pathway

Peng, Qian; Deng, Yan; Yang, Xiling; Leng, Xiangyou; Yang, Yuan; Liu, Hanmin

doi:10.1007/s00431-016-2696-8

Cited by 23 publications

(13 citation statements)

References 38 publications

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“…Many genetic researches demonstrated that several functional single nucleotide polymorphisms (SNPs) within the ADAM17 gene are associated with differences in immune inflammatory response and disease outcomes [25][26][27][28][29][30][31]. To the best of our knowledge, this present study was the first to analyze the clinical relevance of the five polymorphisms (rs55790676, rs12692386, rs11684747, rs1524668 and rs11689958) within the promoter region of ADAM17 to the susceptibility and progression of sepsis.…”

Section: Discussionmentioning

confidence: 96%

“…Several genetic variations of ADAM17 have been demonstrated to be involved in various inflammation-related diseases, such as Kawasaki disease, obesity, Alzheimer's disease and ischemic stroke [25][26][27][28]. A recent study has demonstrated that two functional genetic variations of ADAM17, C-154A and Ser747Leu, contribute to high serum concentration of TNF-α and increased susceptibility to cardiovascular death [29].…”

Section: Introductionmentioning

confidence: 99%

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Association Study Between Promoter Polymorphisms of ADAM17 and Progression of Sepsis

Shao

Chen

et al. 2016

Cell Physiol Biochem

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Background: A disintegrin and metalloproteinase 17 (ADAM17) has been confirmed to play a significant role in the pathogenesis of sepsis. However, little is known about the clinical relevance of ADAM17 polymorphisms to sepsis onset and development. Methods: This study analyzed the associations of five ADAM17 promoter polymorphisms (rs55790676, rs12692386, rs11684747, rs1524668 and rs11689958) with sepsis (370 sepsis cases and 400 controls). Genotyping was performed using pyrosequencing and polymerase chain reaction-length polymorphism method. The ADAM17 expression was measured using the real-time PCR method and the concentrations of related cytokines were detected using enzyme-linked immunosorbent assay. Results: No associations were observed between these polymorphisms and sepsis susceptibility, while the rs12692386GA/GG genotypes were overrepresented among the patients with severe sepsis (P=0.002) or septic shock (P=0.0147) compared to those with sepsis subtype, suggesting a susceptible role of rs12692386A>G in the progression of sepsis. Moreover, ADAM17 expression was increased in the sepsis patients with the rs12692386GA/GG genotypes, accompanied by up-regulation of expression of the ADAM17 substrates (TNF-α, IL-6R and CX3CL1) and pro-inflammatory cytokines (IL-1β and IL-6). Conclusion: The present study has provided potentially valuable clinical evidence that the ADAM17 rs12692386 polymorphism is a functional variant that might be used as a relevant risk estimate for the progression of sepsis.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Association Study Between Promoter Polymorphisms of ADAM17 and Progression of Sepsis

Shao

Chen

et al. 2016

Cell Physiol Biochem

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“…set 2)276/282““xOnouchi et al [92] (Indep. set 3)267/752““xOnouchi et al [95]546/947Yes ( ITPKC )Yes ( ITPKC ) i Yes ( ITPKC ) i ChinesePeng et al [97]223/318Yes ( ITPKC )Yes (ITPKC)NoKhor et al [61]130/568Yes ( ITPKC )xxTaiwaneseChi et al [18]385 (of which 158 trios)/1158NoNoxLin et al [73]280/492Yes ( ITPKC )NoxKuo et al [71]341/1190Yes ( ITPKC )Yes ( ITPKC ) j NoAbove-mentioned studies combined999/2781Yes ( ITPKC )xxKuo et al [68]381/569No k Yes ( ITPKC )xKhor et al [61]438/446Yes ( ITPKC )xxEuropeanKhor et al [61] (GWAS)405/6252 (10)Yes ( ITPKC )xxKhor et al [61] (Replication) 605 trios, 139 siblings l “xxUSOnouchi et al [92]209 triosYes ( ITPKC )Yes ( ITPKC )Yes ( ITPKC )TGF-β pathwayJapaneseCho et al [20]105/303Yes ( SMAD5 )NoxHan ChinesePeng et al [98]392/421Yes ( TGFB2 , SMAD3 , ADAM17 )Yes ( TGFB2 )NoTaiwaneseKuo et al [70]381/569Yes ( SMAD3 )NoNoKoreanChoi et al [21]105/500Yes ( TGFBR2 )Yes ( TGFBR2 )xEuropean descent…”

Section: Geneticsmentioning

confidence: 99%

Dissecting Kawasaki disease: a state-of-the-art review

et al. 2017

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Kawasaki disease (KD) is a pediatric vasculitis with coronary artery aneurysms (CAA) as its main complication. The diagnosis is based on the presence of persistent fever and clinical features including exanthema, lymphadenopathy, conjunctival injection, and changes to the mucosae and extremities. Although the etiology remains unknown, the current consensus is that it is likely caused by an (infectious) trigger initiating an abnormal immune response in genetically predisposed children. Treatment consists of high dose intravenous immunoglobulin (IVIG) and is directed at preventing the development of CAA. Unfortunately, 10–20% of all patients fail to respond to IVIG and these children need additional anti-inflammatory treatment. Coronary artery lesions are diagnosed by echocardiography in the acute and subacute phases. Both absolute arterial diameters and z-scores, adjusted for height and weight, are used as criteria for CAA. Close monitoring of CAA is important as ischemic symptoms or myocardial infarction due to thrombosis or stenosis can occur. These complications are most likely to arise in the largest, so-called giant CAA. Apart from the presence of CAA, it is unclear whether KD causes an increased cardiovascular risk due to the vasculitis itself. Conclusion: Many aspects of KD remain unknown, although there is growing knowledge on the etiology, treatment, and development and classification of CAA. Since children with previous KD are entering adulthood, long-term follow-up is increasingly important. What is known: • Kawasaki disease (KD) is a pediatric vasculitis with coronary artery damage as its main complication. • Although KD approaches its 50th birthday since its first description, many aspects of the disease remain poorly understood. What is new: • In recent years, multiple genetic candidate pathways involved in KD have been identified, with recently promising information about the ITPKC pathway. • As increasing numbers of KD patients are reaching adulthood, increasing information is available about the long-term consequences of coronary artery damage and broader cardiovascular risk.

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“…and activated by transforming growth factor (TGF)-β signaling pathway. TGF-β pathway is involved in in ammation and tissue remodeling mediated by endothelial cells, and immune activation, which support the importance of TGF-βpathway in KD occurrence and outcomes [15,16].CD34 positive cells with enhanced adhesive and homing properties facilitates immune cells homing to the in ammatory sites and mediates in ammatory and immune responses [17].CXCL1, as the chemokine ligand, presents on endothelial surface and mediates immune responses by recruitment of neutrophils and monocytes [18,19].APLN(apelin) is a vasoactive peptide and an endogenous ligand for APJ receptors. APLN/APJ receptor system plays a vital role in regulation of vascular function, including vascular tone, angiogenesis, proliferation, and permeability [20,21].In addition, APLN/APJ system also mediates the anti-in ammatory effects of 1,25(OH)2D3 by reduction of pro-in ammatory mediators and adhesion molecules in LPS-stimulated macrophages [22].…”

Section: Discussionmentioning

confidence: 69%

Expression profile analysis of Differentially Expressed Genes in Human Coronary Artery Endothelial Cells Induced by Serum from Kawasaki Disease: A preliminary study

Fan

Xiao

et al. 2020

Preprint

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Background: Kawasaki disease (KD) leads to coronary artery damage and the etiology of KD is unknown. The present study was designed to explore the differentially expressed genes (DEGs) in KD serum-induced human coronary artery endothelial cells (HCAECs) by RNA-sequence (RNA-seq). Methods: HCAECs were stimulated with serum (15% (v/v)), which were collected from 20 healthy children and 20 KD patients, for 24 hours. DEGs were then detected and analyzed by RNA-seq and bioinformatics analysis. Results: The expression of SMAD1, SMAD6, CD34, CXCL1, PITX2, and APLN was validated by qPCR. 102 genes, 59 up-regulated and 43 down-regulated genes, were significantly differentially expressed in KD groups. GO enrichment analysis showed that DEGs were enriched in cellular response to cytokines, cytokine-mediated signaling pathway, and regulation of immune cells migration and chemotaxis. KEGG signaling pathway analysis showed that DEGs were mainly involved in cytokine−cytokine receptor interaction, chemokine signaling pathway, and TGF−β signaling pathway. Besides, the mRNA expression levels of SMAD1, SMAD6, CD34, CXCL1, and APLN in the KD group were signiﬁcantly up-regulated compared with the normal group, whilePITX2 was significantly down-regulated. Conclusion: 102 DEGs in KD serum-induced HCAECs were identified, and six new targets were proposed as potential indicators of KD.

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Genetic variants of ADAM17 are implicated in the pathological process of Kawasaki disease and secondary coronary artery lesions via the TGF-β/SMAD3 signaling pathway

Cited by 23 publications

References 38 publications

Association Study Between Promoter Polymorphisms of ADAM17 and Progression of Sepsis

Association Study Between Promoter Polymorphisms of ADAM17 and Progression of Sepsis

Dissecting Kawasaki disease: a state-of-the-art review

Expression profile analysis of Differentially Expressed Genes in Human Coronary Artery Endothelial Cells Induced by Serum from Kawasaki Disease: A preliminary study

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