Dataset Information

Genome-wide transcriptome analysis to further understand neutrophil activation and lncRNA transcript profiles in Kawasaki disease.

ABSTRACT: Kawasaki disease (KD) is the most common cause of acquired cardiac disease in children in developed countries. However, little is known regarding the role of transcriptomic targets of KD in the disease progression and development of complications, especially coronary artery aneurysms (CAA). The aim of our study was to identify transcripts affected by KD and their potential role in the disease. We enrolled 37 KD patients and collected blood samples along a comprehensive time-course. mRNA profiling demonstrated an abundance of CD177 transcript in acute KD, and in the intravenous immunoglobulin (IVIG)-resistant group compared to in the IVIG-sensitive group. lncRNA profiling identified XLOC_006277 as the most highly expressed molecule. XLOC_006277 expression in patients at acute stage was 3.3-fold higher relative to patients with convalescent KD. Moreover, XLOC_006277 abundance increased significantly in patients with CAA. XLOC_006277 knockdown suppressed MMP-8 and MMP-9 expression, both associated with heart lesions. Our result suggested that the increase of CD177^pos neutrophils was associated with KD. Moreover, this study provided global long non-coding RNA transcripts in the blood of patients with KD, IVIG-resistant KD, or CAA. Notably, XLOC_006277 abundance was associated with CAA, which might contribute to further understanding of CAA pathogenesis in KD.

SUBMITTER: Ko TM

PROVIDER: S-EPMC6344526 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Genome-wide transcriptome analysis to further understand neutrophil activation and lncRNA transcript profiles in Kawasaki disease.

Ko Tai-Ming TM Chang Jeng-Sheng JS Chen Shih-Ping SP Liu Yi-Min YM Chang Chia-Jung CJ Tsai Fuu-Jen FJ Lee Yi-Ching YC Chen Chien-Hsiun CH Chen Yuan-Tsong YT Wu Jer-Yuarn JY

Scientific reports 20190123 1

Kawasaki disease (KD) is the most common cause of acquired cardiac disease in children in developed countries. However, little is known regarding the role of transcriptomic targets of KD in the disease progression and development of complications, especially coronary artery aneurysms (CAA). The aim of our study was to identify transcripts affected by KD and their potential role in the disease. We enrolled 37 KD patients and collected blood samples along a comprehensive time-course. mRNA profilin ...[more]

PMID: 30674924

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Project description:BackgroundLong noncoding RNAs (lncRNAs) are a recently discovered class of non-protein coding RNAs, which have now increasingly been shown to be involved in a wide variety of biological processes as regulatory molecules. The functional role of many of the members of this class has been an enigma, except a few of them like Malat and HOTAIR. Little is known regarding the regulatory interactions between noncoding RNA classes. Recent reports have suggested that lncRNAs could potentially interact with other classes of non-coding RNAs including microRNAs (miRNAs) and modulate their regulatory role through interactions. We hypothesized that lncRNAs could participate as a layer of regulatory interactions with miRNAs. The availability of genome-scale datasets for Argonaute targets across human transcriptome has prompted us to reconstruct a genome-scale network of interactions between miRNAs and lncRNAs.ResultsWe used well characterized experimental Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) datasets and the recent genome-wide annotations for lncRNAs in public domain to construct a comprehensive transcriptome-wide map of miRNA regulatory elements. Comparative analysis revealed that in addition to targeting protein-coding transcripts, miRNAs could also potentially target lncRNAs, thus participating in a novel layer of regulatory interactions between noncoding RNA classes. Furthermore, we have modeled one example of miRNA-lncRNA interaction using a zebrafish model. We have also found that the miRNA regulatory elements have a positional preference, clustering towards the mid regions and 3' ends of the long noncoding transcripts. We also further reconstruct a genome-wide map of miRNA interactions with lncRNAs as well as messenger RNAs.ConclusionsThis analysis suggests widespread regulatory interactions between noncoding RNAs classes and suggests a novel functional role for lncRNAs. We also present the first transcriptome scale study on miRNA-lncRNA interactions and the first report of a genome-scale reconstruction of a noncoding RNA regulatory interactome involving lncRNAs.

Project description:IntroductionMultiple sclerosis (MS) is a chronic and debilitating inflammatory disease of the central nervous system (CNS), characterized by demyelination and neurodegeneration. Emerging evidence implicates neutrophils in MS pathogenesis, particularly through processes like neutrophil extracellular traps (NETs) formation and degranulation, which may exacerbate inflammation and autoimmunity.MethodsRNA sequencing of peripheral blood neutrophils from MS patients and healthy controls identified differentially expressed genes (DEGs). Pathway enrichment and protein-protein interaction (PPI) analyses highlighted potential biomarkers, validated using reverse transcription quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA).ResultsOur analysis identified 1,968 DEGs in neutrophils from MS patients, comprising 1,068 upregulated and 900 downregulated genes. Pathway enrichment analysis revealed significant involvement of immune processes, including antigen presentation, B and T cell receptor signaling, intracellular signaling cascades, and neutrophil degranulation. Notably, KEGG analysis highlighted a pivotal role for upregulated genes in neutrophil extracellular traps (NETs) formation, a process increasingly associated with autoimmunity. PPI network analysis pinpointed five key hub genes-LCN2, LTF, ELANE, CAMP, and CTSG-as central players in neutrophil-mediated immune modulation. Protein-level validation using ELISA confirmed elevated levels of LCN2, ELANE, CAMP, and CTSG, consistent with transcriptomic findings, further supporting their role as biomarkers. Subsequent RT-qPCR validation demonstrated robust diagnostic potential for these genes, with area under the curve (AUC) values of 0.952 (LCN2), 0.827 (LTF), 0.968 (ELANE), 0.950 (CAMP), and 0.862 (CTSG).DiscussionThese findings uncover a previously underappreciated role for neutrophils in MS pathogenesis, driven by alterations in gene expression linked to immune modulation and NET formation. The identified biomarkers, particularly ELANE and LCN2, demonstrate strong diagnostic potential, offering a new avenue for non-invasive MS diagnostics. Beyond clinical utility, this study highlights the importance of neutrophil-driven immune responses in MS, providing mechanistic insights into the complex interplay between innate and adaptive immunity in demyelinating diseases. Furthermore, these findings suggest that targeting neutrophil-specific processes, such as NETs formation and degranulation, could mitigate inflammatory damage and provide novel therapeutic approaches for MS treatment. These results lay the groundwork for future studies exploring therapeutic strategies targeting neutrophil functions in MS.

Dataset Information

Genome-wide transcriptome analysis to further understand neutrophil activation and lncRNA transcript profiles in Kawasaki disease.

Publications

Genome-wide transcriptome analysis to further understand neutrophil activation and lncRNA transcript profiles in Kawasaki disease.

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