Park, K. S. Shin, and W. K. Youn, “Polymorphism of matrix metalloproteinase-3 promoter gene as a risk factor for coronary artery lesions in Kawasaki disease,”, C. Shimizu, T. Matsubara, Y. Onouchi et al., “Matrix metalloproteinase haplotypes associated with coronary artery aneurysm formation in patients with Kawasaki disease,”, J. Gao, H. Y. Wang, N. J. Wu, and S. H. Zhang, “Relationship between fibrinogen B, J. C. Burns, C. Shimizu, E. Gonzalez et al., “Genetic variations in the receptor-ligand pair, M. Mamtani, T. Matsubara, C. Shimizu et al., “Association of, W. B. Breunis, M. H. Biezeveld, J. Geissler et al., “Polymorphisms in chemokine receptor genes and susceptibility to Kawasaki disease,”, W. K. Jhang, M. J. Kang, H. S. Jin et al., “The, Y. C. Huang, Y. J. Lin, J. S. Chang et al., “Single nucleotide polymorphism rs2229634 in the, J. J. Sheu, Y. J. Lin, J. S. Chang et al., “Association of, J. Yang, C. R. Li, Y. Investigators propose that mediators such as tumor necrosis factor (TNF), interleukin (IL)-1B, interferon (INF) and IL-6 produced by activated T-cells and macrophages promote vascular injury. One study indicated that MMPs and TIMPs were in a state of imbalance in KD patients [122]. Additionally, the mutation of CASP3 (rs113420705) can reduce the binding of NFAT to the DNA surrounding the SNP. Exercise stress test may be considered in select patients. NF-AT signaling and leukocyte interactions ( Some studies have indicated that NF-κB is excessively activated in the acute phase of KD and the inhibition of NF-κB can reduce the generation of inflammatory cytokines which plays important roles in vascular damage of KD [179, 180]. Other studies [167, 168] also stated that CASP3 plays an important role in the execution phase of apoptosis of immune cells in KD. All of these proteins (encoded by genes) are interrelated, forming a large network. Kimura disease, Churg-Stauss vasculitis, Kawasaki disease)" Malignancies (eg. KD is more common in patients of Asian descent. As a result of this, the cells are mo… The earliest pathological change reported in the vessel wall is subendothelial accumulation of T-cells, mononuclear cells, macrophages and monocytes. It is activated in response to signals that lead to cell growth, differentiation, apoptosis, and other events. NFATs are nuclear factors of activated T cells. The NFAT signal is activated in T cell and can promote the expression of the immune-related genes. Stress test may be needed in teenagers who had a history of previous coronary involvement before participating in competitive sports. It provides a comprehensive set of functional annotation tools for investigators to understand biological meaning behind large list of genes. CD40 signaling can also enhance the expression of cytokines, chemokines, matrix metalloproteinases, adhesion molecules, platelet-activating factors, prostaglandin E2, vascular endothelial growth factor, and NO. The abstracted genes involved in significant pathways are summarized in Table 3. Additionally, various inflammatory cytokines and chemokines [107, 108], matrix metalloproteinases, nitric oxide production [109], autoantibody production [110, 111], and adhesive molecule expression [112, 113] are also overactivated in the acute stage of KD which are considered to facilitate vascular endothelial inflammation and then participate in the pathogenesis of KD and CAL formation. Endogenous tissue inhibitors of metalloproteinases (TIMPs) such as TIMP1, TIMP2, and TIMP3 can reduce excessive proteolytic ECM degradation by MMPs. The etiology of KD is unknown. NF-AT signaling was first mentioned to be associated with regulation of ITPKC in the KD. Many suspicious genes related to innate and acquired immune functions or to vascular remodeling have been studied [15, 17–19]. It almost always affects young children. Acute myocardial infarction may occur during the acute phase due to vasculitis and perivasculitis. All of these physiological processes occur in KD. With the disease folders, representing over 112 human diseases annotated by GeneGo, these 76 genes were mainly related to autoimmune diseases and some kinds of vascular inflammatory diseases. Kawasaki Disease (KD) vasculopathy, which most significantly affects the coronary arteries, is characterized by three linked pathological processes: necrotizing arteritis, subacute/chronic (SA/C) vasculitis, and luminal myofibroblastic proliferation (LMP). Candidate gene studies identified genes associated with KD. Kawasaki disease is a condition that mainly affects children under the age of 5. The shape alters the properties of the cells, causing then to become more rigid and less flexible. The results indicate that CASP3, IL18, BLK, FCGR2B, FCGR2A, CRP, CCR5, CCL5, CCR3, CCL3L1, TNFRSF1A, TNF, IL4, ERAP1, LTA, CD40, NOD1, CTLA4, NLRP1, TGFBR2, SMAD3, TGFB2, VEGFA, KDR, and CCR2 are associated according to experimental evidence, with involvement in many signaling pathways; TNF was the key of nodes, linking to CRP, IL-4, CD40, CD40LG, IL-18, IL-10, and so on. The inclusion criteria of genes were those who have significant association with KD contributed to susceptibility, vascular lesions, resistance to initial IVIG treatment, late diagnosis of KD, and incomplete KD. Gene ontology category and pathways were analyzed for relationships among these statistically significant genes. The body fluids are primarily composed of sodium and water . Dr. Cornelia Franz answered. CD40 signaling leads to isotype switching and autoantibody production in B cells and in T-cell priming, altering TCR expression through the expression and nuclear translocation of recombinases, which increases the risk of developing autoimmunity [173]. Methods. It is suggested that the Ca2+/NFAT pathway may involve in the pathological processes of KD. In the immune system, NFATs have pivotal roles in the development and function of immune organs and regulate numerous physiological processes. Kawasaki disease (KD) is the leading cause of acquired heart disease in children in the United States. Some Rights Reserved. Sign up here as a reviewer to help fast-track new submissions. NFATs are mainly Ca2+-sensitive transcription factors that regulate gene transcription in response to intracellular Ca2+ signals. Dr. John Goldman answered. In B cells and T-cell, CD40 signaling leads to isotype switching, autoantibody production, and altering TCR expression. What is thought to be the underlying pathophysiology of SIDS? Activated by NFAT signal in T cell, IL-4 activates nearby B cells that express corresponding receptor, IL-4R. IL-4, CD40, and CD40L, which are enriched in the pathway of NF-AT signaling and leukocyte interactions and play a crucial role in the immune response and remodeling process, are located in the center position of the network (analysed by STRING) and are closely linked with the other factors. value = 2.28 × 10−5) in the immune response cause our great concern. IL-4 and IL-13, in turn, activate epithelial cells and/or fibroblasts to release eosinophil-activating cytokines, such as chemokine ligand 11 (Eotaxin). It has also been reported to cleave the inositol 1,4,5-triphosphate receptor, type 1 (ITPR1) in apoptotic T cells (ITPR1 is a receptor for inositol 1,4,5-trisphosphate (IP3), a substrate for ITPKC in T cells [165]). Contributor Information and Disclosures . Kawasaki disease is a vasculitis of medium-sized arteries, most significantly the coronary arteries, which are involved in about 20% of untreated patients. in other cells. Clinical manifestations of KD include prolonged fever (1-2 weeks, mean 10-11 days), conjunctival infection, oral lesions, polymorphous skin rashes, extremity changes, and cervical lymphadenopathy, all of which comprise diagnostic criteria [3]. Hodgkin lymphoma, IgE myeloma)" Cutaneous diseases (eg. The need for further echocardiograms is determined by the presence or absence of coronary involvement. GeneGo MetaCore (http://www.genego.com/, version: 6.5) was used to analyze the pathways of these significant genes. Mask et al., “IgA plasma cell infiltration of proximal respiratory tract, pancreas, kidney, and coronary artery in acute Kawasaki disease,”, C. Galeotti, J. Bayry, I. Kone-Paut, and S. V. Kaveri, “Kawasaki disease: aetiopathogenesis and therapeutic utility of intravenous immunoglobulin,”, J. Kimura, H. Takada, A. Nomura et al., “Th1 and Th2 cytokine production is suppressed at the level of transcriptional regulation in Kawasaki disease,”, H. C. Kuo, C. L. Wang, C. D. Liang et al., “Association of lower eosinophil-related T helper 2 (Th2) cytokines with coronary artery lesions in Kawasaki disease,”, C. L. Wang, Y. T. Wu, C. J. Lee, H. C. Liu, L. T. Huang, and K. D. Yang, “Decreased nitric oxide production after intravenous immunoglobulin treatment in patients with Kawasaki disease,”, M. Fujieda, R. Karasawa, H. Takasugi et al., “A novel anti-peroxiredoxin autoantibody in patients with Kawasaki disease,”, J. K. Chun, T. J. Lee, K. M. Choi, K. H. Lee, and D. S. Kim, “Elevated anti-, T. Kobayashi, H. Kimura, Y. Okada et al., “Increased CD11b expression on polymorphonuclear leucocytes and cytokine profiles in patients with Kawasaki disease,”, Y. Mitani, H. Sawada, H. Hayakawa et al., “Elevated levels of high-sensitivity C-reactive protein and serum amyloid-A late after Kawasaki disease: association between inflammation and late coronary sequelae in Kawasaki disease,”, A. Bonnefoy and C. Legrand, “Proteolysis of subendothelial adhesive glycoproteins (fibronectin, thrombospondin, and von Willebrand factor) by plasmin, leukocyte cathepsin G, and elastase,”, H. Morgan and P. A. Hill, “Human breast cancer cell-mediated bone collagen degradation requires plasminogen activation and matrix metalloproteinase activity,”, K. Imai, H. Shikata, and Y. Okada, “Degradation of vitronectin by matrix metalloproteinases-1, -2, -3, -7 and -9,”, S. D. Shapiro, “Matrix metalloproteinase degradation of extracellular matrix: biological consequences,”, S. Netzel-Arnett, D. J. Mitola, S. S. Yamada et al., “Collagen dissolution by keratinocytes requires cell surface plasminogen activation and matrix metalloproteinase activity,”, K. Sakata, K. Hamaoka, S. Ozawa et al., “Matrix metalloproteinase-9 in vascular lesions and endothelial regulation in Kawasaki disease,”, J. Verstappen and J. W. von den Hoff, “Tissue inhibitors of metalloproteinases (TIMPs): their biological functions and involvement in oral disease,”, A. R. Hannas, J. C. Pereira, J. M. Granjeiro, and L. Tjäderhane, “The role of matrix metalloproteinases in the oral environment,”, H. Senzaki, S. Masutani, J. Kobayashi et al., “Circulating matrix metalloproteinases and their inhibitors in patients with Kawasaki disease,”, E. Serfling, F. Berberich-Siebelt, A. Avots et al., “NFAT and NF-, F. Macian, “NFAT proteins: key regulators of T-cell development and function,”, F. Rusnak and P. Mertz, “Calcineurin: form and function,”, F. Macián, C. López-Rodríguez, and A. Rao, “Partners in transcription: NFAT and AP-1,”, M. Lee and J. Patients with regression of the coronary aneurysms remain at risk for stenosis because the affected area may be less compliant. Tables. This disease is considered a kind of systemic vasculitis syndrome, and primarily invades the medium-sized muscular arteries, including coronary arteries. Ashraf Aly and Soham Dusgupta Dept. ITPKC is a kinase of inositol 1,4,5-triphosphate (IP3) which is a second messenger molecule that releases calcium from the endoplasmic and sarcoplasmic reticulum. Thereby, it is a positive regulatory factor of NFAT signal. It may be used as a diagnostic and interventional tool. Cardiac failure this is the critical factor that determines morbidity and mortality in... Four ( except NFAT5 ) of these significant genes are mainly Ca2+-sensitive transcription that... Showed that many MMPs were highly expressed in the acute phase but may be.. As TIMP1, TIMP2, and primarily invades the medium-sized muscular arteries, including the arteries... Or a disease such as leukotrienes and prostaglandins, terms, and pericarditis determine follow up echo should be for! 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Seen in boys younger than five years are hospitalized with kawasaki disease still! Surgical intervention may be less compliant changes on a clinical diagnosis the important features in KD small... Pathway showed the biological pathways and diseases these genes and implied the importance of this pathway ( Enrichment Score 15.91...
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