Differentially expressed genes in peripheral blood of patients with dermatomyositis complicated by interstitial lung disease or malignant tumors

Bovine tuberculosis, caused by infection with members of the Mycobacterium tuberculosis complex, particularly Mycobacterium bovis, is a major endemic disease affecting cattle populations worldwide, despite the implementation of stringent surveillance and control programs in many countries. The development of high-throughput functional genomics technologies, including RNA sequencing, has enabled detailed analysis of the host transcriptome to M. bovis infection, particularly at the macrophage and peripheral blood level. In the present study, we have analysed the transcriptome of bovine whole peripheral blood samples collected at −1 week pre-infection and +1, +2, +6, +10, and +12 weeks post-infection time points. Differentially expressed genes were catalogued and evaluated at each post-infection time point relative to the −1 week pre-infection time point and used for the identification of putative candidate host transcriptional biomarkers for M. bovis infection. Differentially expressed gene sets were also used for examination of cellular pathways associated with the host response to M. bovis infection, construction of de novo gene interaction networks enriched for host differentially expressed genes, and time-series analyses to identify functionally important groups of genes displaying similar patterns of expression across the infection time course. A notable outcome of these analyses was identification of a 19-gene transcriptional biosignature of infection consisting of genes increased in expression across the time course from +1 week to +12 weeks post-infection.

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Plasma-Derived Exosomal hsa-miR-4488 and hsa-miR-1228-5p: Novel Biomarkers for Dermatomyositis-Associated Interstitial Lung Disease with Anti-Melanoma Differentiation-Associated Protein 5 Antibody-Positive Subset

BioMed Research International ◽

10.1155/2021/6676107 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Danli Zhong ◽

Chanyuan Wu ◽

Dong Xu ◽

Jingjing Bai ◽

Qian Wang ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

Target Genes ◽

Homo Sapiens ◽

Differentially Expressed ◽

Transmission Electron ◽

Exosomal Mirnas ◽

Differentially Expressed Mirnas ◽

Novel Biomarkers ◽

And Gender

The present study is aimed at profiling circulating exosome-derived microRNAs (miRNAs/miRs) from patients with dermatomyositis (DM), in particular those complicated with interstitial lung disease (ILD) with anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive. Fifteen participants were enrolled, including five patients with DM complicated with ILDs prior to treatment with circulating anti-MDA5 antibody-positive status [DM-ILD-MDA5 Ab(+)], five DM patients without ILDs who were negative for 16 detectable myositis-specific antibodies [DM-nonILD-MSA16(-)], and five age- and gender-matched healthy donor controls (HCs). The characteristics of the exosomes extracted by Ribo™ Exosome Isolation Reagent were identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and flow cytometry. Differentially expressed miRNAs, determined by next-generation deep sequencing, were identified through the criteria of ∣ log 2 fold change ∣ ≥ 1 and P < 0.01 . A total of 38 miRNAs were significantly upregulated in exosomes from patients with DM-ILD-MDA5 Ab(+) compared to those from HC, while 21 miRNAs were significantly downregulated. Compared to exosomes derived from patients with DM-nonILD-MSA16(-), 51 miRNAs were significantly upregulated and 33 miRNAs were significantly downregulated from patients with DM-ILD-MDA5 Ab(+). A total of 73 exosomal miRNAs were significantly differentially expressed between DM-nonILD-MSA16(-) and HC. In particular, two miRNAs, Homo sapiens- (hsa-) miR-4488 and hsa-miR-1228-5p, were common differentially expressed miRNAs among three comparisons. GO and KEGG analyses suggested that several pathways may contribute the pathogenesis of DM-ILD-MDA5 Ab(+) and DM-nonILD-MSA16(-), while PPI network analysis of hsa-miR-4488 and hsa-miR-1228-5p indicated that their predicted target genes, DExD-box helicase 39B and MDM2, may be involved in the mechanisms of DM-ILD-MDA5 Ab(+).

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Genes related to maintenance of autophagy and successful aging

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20180142 ◽

2018 ◽

Vol 76 (12) ◽

pp. 831-839

Author(s):

Carolina Fioroto Chaves ◽

Diego Robles Mazzotti ◽

Maysa Seabra Cendoroglo ◽

Luiz Roberto Ramos ◽

Sergio Tufik ◽

...

Keyword(s):

Cell Survival ◽

Differentially Expressed Genes ◽

Expression Profile ◽

Peripheral Blood ◽

Successful Aging ◽

Oldest Old ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Expression Of Genes ◽

Transcriptional Process

ABSTRACT Considering aging as a phenomenon in which there is a decline in essential processes for cell survival, we investigated the autophagic and proteasome pathways in three different groups: young, older and oldest old male adults. The expression profile of autophagic pathway-related genes was carried out in peripheral blood, and the proteasome quantification was performed in plasma. No significant changes were found in plasma proteasome concentrations or in correlations between proteasome concentrations and ages. However, some autophagy- and/or apoptosis-related genes were differentially expressed. In addition, the network and enrichment analysis showed an interaction between four of the five differentially expressed genes and an association of these genes with the transcriptional process. Considering that the oldest old individuals maintained both the expression of genes linked to the autophagic machinery, and the proteasome levels, when compared with the older group, we concluded that these factors could be considered crucial for successful aging.

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P6288Autoantibodies in heart failure associate with disease severity and differentially expressed genes in apoptotic, fibrotic, and hypoxia pathways in cardiomyocytes

European Heart Journal ◽

10.1093/eurheartj/ehz746.0886 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

J Myers ◽

C Sandel ◽

K Alvarez ◽

L Garman ◽

K White ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Cardiac Hypertrophy ◽

Dilated Cardiomyopathy ◽

Rna Sequencing ◽

Differentially Expressed Genes ◽

Peripheral Blood ◽

Differentially Expressed ◽

Heart Cell ◽

Cardiac Myosin

Abstract Background Previous studies suggest that autoantibodies against cardiac myosin lead to dilated cardiomyopathy (DCM). Anti-cardiac myosin antibodies cross-react with the beta adrenergic receptor (βAR) and signal cAMP-dependent protein kinase A (PKA) in cardiomyocytes leading to apoptosis, fibrosis, dilated cardiomyopathy and arrhythmias. Purpose To determine if cross-reactive anti-cardiac myosin/anti-βAR autoantibodies which signal cardiomyocytes through PKA might play a role to establish DCM by promoting remodeling, apoptosis, and fibrosis. Methods Forty-one adults with DCM were enrolled <6 months from symptom onset and followed for 12 months. Serum and myocarditis/DCM-derived human mAb were analyzed by ELISA for autoantibodies, and a PKA assay measured anti-HCM/βAR antibody-mediated signaling of cardiomyocytes (ATCC primary heart cell line H9c2). The top 50 genes differentially expressed in the cardiomyocytes treated with sera or human mAb were identified and compared to genes differentially expressed in blood of DCM patients to identify shared disease-specific genes. Results Anti-HCM autoantibodies including autoantibody responses against 32 overlapping synthetic peptides of the S2 fragment of HCM were significantly elevated in patients whose ejection fraction did not improve over 1-year compared to those with improved ejection fraction. The human mAb confirmed our results with HCM, βAR, specific HCM peptides, and PKA signaling. RNA sequencing revealed differentially expressed genes in serum/mAb-treated cardiomyocytes compared to genes identified after RNA sequencing of peripheral blood of patients (n=10) with DCM for >1 year from onset. A primary heart cell line (H9c2-ATCC) treated with myocarditis/DCM patient sera or human mAb revealed differentially expressed genes associated with cardiac hypertrophy and heart failure, and included inflammasome component NLRP3 and complement factor H. Ingenuity Pathway Analyses revealed 27, 7, and 1 differentially expressed genes related to apoptosis, fibrosis, and hypoxia, respectively. Gene expression of CASZ1, a transcription factor important in protection against DCM, was strongly correlated with PKA signaling (r=0.89). The KDM6B gene for lysine demethylase associated with hypoxia and apoptosis pathways and was shared between cardiomyocyte and peripheral blood analysis of DCM patients. Overall, 5 genes were shared in heart failure vs in vitro Ab-treated cardiomyocyte RNA sequencing analysis: CYP4F3, KDM6B, MBOAT7, SMAP2, and DDIT4, which affects phosphorylation of mTOR to promote autophagy and cell death, cardiac hypertrophy and dysfunction. Conclusions Significantly higher responses to cardiac myosin in patients with DCM were related to lack of left ventricular function improvement and to differential expression of genes promoting apoptosis, fibrosis and disease severity. These studies identify autoantibody-directed gene signaling as a potential novel therapeutic target in DCM. Acknowledgement/Funding National Heart, Lung, and Blood Institute, Bethesda, MD, USA

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Comparative transcriptomic analysis of porcine peripheral blood reveals differentially expressed genes from the cytokine–cytokine receptor interaction pathway related to health status

Genome ◽

10.1139/gen-2017-0074 ◽

2017 ◽

Vol 60 (12) ◽

pp. 1021-1028 ◽

Cited By ~ 2

Author(s):

M.H. Ye ◽

H. Bao ◽

Y. Meng ◽

L.L. Guan ◽

P. Stothard ◽

...

Keyword(s):

Health Status ◽

Differentially Expressed Genes ◽

Peripheral Blood ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Cytokine Receptor ◽

Functional Enrichment ◽

Differentially Expressed ◽

Receptor Interaction ◽

Marker Genes

While some research has looked into the host genetic response in pigs challenged with specific viruses or bacteria, few studies have explored the expression changes of transcripts in the peripheral blood of sick pigs that may be infected with multiple pathogens on farms. In this study, the architecture of the peripheral blood transcriptome of 64 Duroc sired commercial pigs, including 18 healthy animals at entry to a growing facility (set as a control) and 23 pairs of samples from healthy and sick pen mates, was generated using RNA-Seq technology. In total, 246 differentially expressed genes were identified to be specific to the sick animals. Functional enrichment analysis for those genes revealed that the over-represented gene ontology terms for the biological processes category were exclusively immune activity related. The cytokine–cytokine receptor interaction pathway was significantly enriched. Nine functional genes from this pathway encoding members (as well as their receptors) of the interleukins, chemokines, tumor necrosis factors, colony stimulating factors, activins, and interferons exhibited significant transcriptional alteration in sick animals. Our results suggest a subset of novel marker genes that may be useful candidate genes in the evaluation and prediction of health status in pigs under commercial production conditions.

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Identification of Potential ceRNA Network and Patterns of Immune Cell Infiltration in Systemic Sclerosis-Associated Interstitial Lung Disease

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.622021 ◽

2021 ◽

Vol 9 ◽

Author(s):

Qiuhong Wu ◽

Yang Liu ◽

Yan Xie ◽

Shixiong Wei ◽

Yi Liu

Keyword(s):

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Immune Cells ◽

Regulatory Network ◽

Target Genes ◽

Immune Cell ◽

Differentially Expressed ◽

Immune Cell Infiltration ◽

Overlapping Genes

PurposeSystemic sclerosis-associated interstitial lung disease (SSc-ILD) is one of the most severe complications of systemic sclerosis (SSc) and is the leading cause of SSc-related deaths. However, the precise pathogenesis of pulmonary fibrosis in SSc-ILD remains unknown. This study aimed to evaluate the competing endogenous RNA (ceRNA) regulatory network and immune cell infiltration patterns in SSc-ILD.MethodsOne microRNA (miRNA) and three messenger RNA (mRNA) microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. Then, the differentially expressed miRNAs (DEmiRs) and mRNAs (DEMs) between SSc-ILD patients and normal controls were identified, respectively, followed by the prediction of the target genes and target lncRNAs of DEmiRs. The overlapping genes between DEmiRs target genes and DEMs were identified as core mRNAs to construct the ceRNA network. In addition, the “Cell Type Identification by Estimating Relative Subsets of Known RNA Transcripts (CIBERSORT)” algorithm was used to analyze the composition of infiltrating immune cells in lung tissues of SSc-ILD patients and controls, and differentially expressed immune cells were recognized. The correlation between immune cells and core mRNAs was evaluated by Pearson correlation analysis.ResultsTotally, 42 SSc-ILD lung tissues and 18 normal lung tissues were included in this study. We identified 35 DEmiRs and 142 DEMs and predicted 1,265 target genes of DEmiRs. Then, 9 core mRNAs related to SSc-ILD were recognized, which were the overlapping genes between DEmiRs target genes and DEMs. Meanwhile, 9 DEmiRs related to core mRNAs were identified reversely, and their target lncRNAs were predicted. In total, 9 DEmiRs, 9 core mRNAs, and 51 predicted lncRNAs were integrated to construct the ceRNA regulatory network of SSc-ILD. In addition, 9 types of immune cells were differentially expressed in lung tissues between SSc-ILD patients and controls. Some core mRNAs, such as COL1A1, FOS, and EDN1, were positively or negatively correlated with the number of infiltrating immune cells.ConclusionThis is the first comprehensive study to construct the potential ceRNA regulatory network and analyze the composition of infiltrating immune cells in lung tissues of SSc-ILD patients, which improves our understanding of the pathogenesis of SSc-ILD.

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Transcriptome Sequencing Identifies PLAUR as an Important Player in Patients With Dermatomyositis-Associated Interstitial Lung Disease

Frontiers in Genetics ◽

10.3389/fgene.2021.784215 ◽

2021 ◽

Vol 12 ◽

Author(s):

Juan Chen ◽

Ruixian Zhang ◽

Min Xie ◽

Chunyan Luan ◽

Xiaolan Li

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Healthy Controls ◽

Biological Processes ◽

Blood Samples ◽

Important Player ◽

Key Genes

Dermatomyositis (DM), an inflammatory disorder, is often associated with interstitial lung disease (ILD). However, the underlying mechanism remains unclear. Our study performed RNA sequencing (RNA-seq) and integrative bioinformatics analysis of differentially expressed genes (DEGs) in patients with dermatomyositis-associated interstitial lung disease (DM-ILD) and healthy controls. A total of 2,018 DEGs were identified between DM-ILD and healthy blood samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that DEGs were mainly involved in immune- and inflammatory-related biological processes and pathways. Disease ontology (DO) enrichment analysis identified 35 candidate key genes involved in both skin and lung diseases. Meanwhile, a total of 886 differentially expressed alternative splicing (AS) events were found between DM-ILD and healthy blood samples. After overlapping DEGs with differential AS genes, the plasminogen activator and urokinase receptor (PLAUR) involved in immune-related biological processes and complement and coagulation cascades was screened and identified as the most important gene associated with DM-ILD. The protein–protein interaction (PPI) network revealed that PLAUR had interactions with multiple candidate key genes. Moreover, we observed that there were significantly more neutrophils and less naive B cells in DM-ILD samples than in healthy samples. And the expression of PLAUR was significantly positively correlated with the abundance of neutrophils. Significant higher abundance of PLAUR in DM-ILD patients than healthy controls was validated by RT-qPCR. In conclusion, we identified PLAUR as an important player in regulating DM-ILD by neutrophil-associated immune response. These findings enrich our understanding, which may benefit DM-ILD patients.

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Diabetes-specific modulation of peripheral blood gene expression signatures in colorectal cancer

Current Molecular Medicine ◽

10.2174/1566524020666200504084626 ◽

2020 ◽

Vol 20 ◽

Author(s):

Zsuzsanna Molnár ◽

Zsófia Bánlaki ◽

Anikó Somogyi ◽

Zoltán Herold ◽

Magdolna Herold ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Differentially Expressed Genes ◽

Peripheral Blood ◽

Expression Patterns ◽

Enrichment Analysis ◽

Colorectal Carcinogenesis ◽

Differentially Expressed ◽

Blood Leukocytes ◽

Significant Expression

Background: Type 2 diabetes (T2DM) and colorectal cancer (CRC) are both known to modulate gene expression patterns in peripheral blood leukocytes (PBLs). Objective : As T2DM has been shown to increase the incidence of CRC, we were prompted to check whether diabetes affects mRNA signatures in PBLs isolated from CRC patients. Methods : 22 patients were recruited to the study and classified into four cohorts (healthy controls; T2DM; CRC; CRC and T2DM). Relative expression levels of 573 cell signaling gene transcripts were determined by reverse transcription real-time PCR assays run on low-density OpenArray platforms. Enrichment analysis was performed with the g:GOSt profiling tool to order differentially expressed genes into functional pathways. Results : 49 genes were found to be significantly up- or downregulated in tumorous diabetic individuals as compared to tumor-free diabetic controls, while 11 transcripts were differentially regulated in patients with CRC versus healthy, tumor-free and non-diabetic controls. Importantly, these gene sets were completely distinct, implying that diabetes exerts profound influence on the transcription of signaling genes in CRC. The top 5 genes showing most significant expression differences in both contexts were PCK2, MAPK9, CCND1, HMBS, TLR3 (p≤ 0.0040) and CREBBP, PPIA, NFKBIL1, MDM2 and SELPLG (p0.0121), respectively. Functional analysis revealed that most significantly affected pathways were cytokine, interleukin and PI3K/Akt/mTOR signaling cascades as well as mitotic regulation. Conclusions : We propose that differentially expressed genes listed above might be potential biomarkers of CRC and should be studied further on larger patient groups. Diabetes might promote colorectal carcinogenesis by impairing signaling pathways in PBLs.

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Peripheral blood leucocyte telomere length is associated with progression of interstitial lung disease in systemic sclerosis

Thorax ◽

10.1136/thoraxjnl-2020-215918 ◽

2021 ◽

pp. thoraxjnl-2020-215918

Author(s):

Shuo Liu ◽

Melody P Chung ◽

Brett Ley ◽

Sarah French ◽

Brett M Elicker ◽

...

Keyword(s):

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Telomere Length ◽

San Francisco ◽

Longitudinal Analysis ◽

Peripheral Blood ◽

Peripheral Blood Leucocyte ◽

Increased Risk ◽

The University

BackgroundPeripheral blood leucocyte telomere length (PBL-TL) is associated with outcomes in patients with idiopathic pulmonary fibrosis. Whether PBL-TL is associated with progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is unknown.MethodsA retrospective observational cohort study was performed using prospectively collected data from 213 patients with SSc followed at the University of California San Francisco (UCSF) Scleroderma Center. PBL-TL was measured by quantitative PCR of DNA isolated from peripheral blood. Associations between PBL-TL and pulmonary function test trends in patients with SSc-ILD were assessed by longitudinal analysis using Generalised Linear Mixed Models. Findings were validated in a cohort of 61 patients with SSc-ILD enrolled in the Stanford University Scleroderma Center database.ResultsPatients with UCSF SSc with ILD were found to have shorter PBL-TL compared with those without ILD (6554±671 base pairs (bp) vs 6782±698 bp, p=0.01). Shorter PBL-TL was associated with the presence of ILD (adjusted OR 2.1 per 1000 bp TL decrease, 95% CI [1.25 to 3.70], p=0.006). PBL-TL was shorter in patients with SSc-ILD lacking SSc-specific autoantibodies compared with seropositive subjects (6237±647 bp vs 6651±653 bp, p=0.004). Shorter PBL-TL was associated with increased risk for lung function deterioration with an average of 67 mL greater loss in per year for every 1000 bp decrease in PBL-TL in the combined SSc-ILD cohorts (longitudinal analysis, adjusted model: 95% CI −104 mL to −33 mL, p<0.001).ConclusionsThese findings suggest that telomere dysfunction may be associated with SSc-ILD progression and that PBL-TL measurement may be useful for stratifying risk for SSc-ILD progression.

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