scholarly journals Systemic Proteomic Analysis Reveals Distinct Exosomal Proteins Profiles in Rheumatoid Arthritis

2020 ◽  
Author(s):  
Qiu Qin ◽  
Ronghua SONG ◽  
Peng DU ◽  
Chaoqun GAO ◽  
Qiuming YAO ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Regulatory Networks ◽  
Matrix Protein ◽  
Complex Disease ◽  
Interaction Network ◽  
Nf Kappa B ◽  
Regulatory Pathways ◽  
And Gender ◽  
Underlying Mechanisms ◽  
Pathway Analyses

Abstract BackgroundRheumatoid arthritis (RA) is a heterogeneous and complex disease characterized by autoantibodies production and inflammation of the synovium. Its underlying mechanisms remain elusive. In recent years, exosomes have emerged as non-invasive biomarkers in diverse diseases. Due to its various inflammatory and immunological functions, some studies highlighted abnormalities of exosomes in RA, but fewer have paid attention to the broad spectrum of potential systemic markers of RA. The aim of this study was to identify exosomal candidate proteins in the pathogenesis of RA using systemic proteomic method. MethodsTotally 12 specimens of plasma from 6 RA patients and 6 age-and gender-matched controls from the Chinese population were obtained for nanoscale liquid chromatography coupled to tandem mass spectrometry (nano-LC-MS/MS) analysis to identify differentially expressed proteins (DEPs) in exosomes. Gene ontology (GO), protein interaction network (PPI) and KEGG pathway analyses were used in subcellular localization analysis. ResultsA total of 278 exosomal proteins were detected. Among them, 32 proteins were significantly upregulated (FC≥2.0 and P<0.05) and 5 proteins were downregulated (FC≤0.5 and P<0.05). Most of these DEPs were immunoglobullins (Igs). Bioinformatics analysis indicated that these Igs are involved in inflammatory response of RA through diverse immune regulatory pathways, such as NF-kappa B signaling pathway. PPI analysis revealed that transthyretin (TTR, P02766), angiotensinogen (AGT, P01019), lipopolysaccharide-binding protein (LBP, P18428), monocyte differentiation antigen CD14 (CD14, P08571), cartilage oligomeric matrix protein (COMP, P49747), serum amyloid P (SAP/APCS, P02743) and tenascin (TNC, P24821) can interact with each other or may form a regulatory networks. Subsequently, these cross-linked proteins may mainly involve in the NF-kappa B signaling pathway or inflammatory-related pathways to mediate the onset of RA. Noteworthy, among these exosomal DEPs, the complex composed of LBP and CD14 is involved in NF-kappa B signaling pathway, resulting in promoted expression of IL-8, TNF-α, and eventually leading to the development of RA.ConclusionsOur findings suggest distinct plasmic exosomal protein profiles in RA patients. These proteins not only take important parts in the vicious circle in the pathogenic process of RA, but also serve as novel biomarkers in RA diagnosis and prognosis.

scholarly journals Systemic Proteomic Analysis Reveals Distinct Exosomal Protein Profiles in Rheumatoid Arthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Qiu Qin ◽  
Ronghua Song ◽  
Peng Du ◽  
Chaoqun Gao ◽  
Qiuming Yao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Matrix Protein ◽  
Complex Disease ◽  
Protein Profiles ◽  
Monocyte Differentiation ◽  
Diagnosis And Prognosis ◽  
Tnf Α ◽  
Novel Biomarkers ◽  
And Gender ◽  
Amyloid P

Objective. Rheumatoid arthritis (RA) is a complex disease with unknown pathogenesis. In recent years, fewer have paid attention to the broad spectrum of systemic markers of RA. The aim of this study was to identify exosomal candidate proteins in the pathogenesis of RA. Methods. Totally, 12 specimens of plasma from 6 RA patients and 6 age- and gender-matched controls from the Chinese population were obtained for nanoscale liquid chromatography coupled to tandem mass spectrometry (nano-LC-MS/MS) analysis to identify exosomal profiles. Results. A total of 278 exosomal proteins were detected. Among them, 32 proteins were significantly upregulated ( FC ≥ 2.0 and P < 0.05 ) and 5 proteins were downregulated ( FC ≤ 0.5 and P < 0.05 ). Bioinformatics analysis revealed that transthyretin (TTR), angiotensinogen (AGT), lipopolysaccharide-binding protein (LBP), monocyte differentiation antigen CD14 (CD14), cartilage oligomeric matrix protein (COMP), serum amyloid P (SAP/APCS), and tenascin (TNC) can interact with each other. Subsequently, these cross-linked proteins may be mainly involved in the inflammatory-related pathways to mediate the onset of RA. Noteworthy, the LBP/CD14 complex can promote the expression of IL-8 and TNF-α, eventually leading to the development of RA. Conclusions. Our findings suggest distinct plasmatic exosomal protein profiles in RA patients. These proteins not only take important parts in the vicious circle in the pathogenic process of RA but also serve as novel biomarkers in RA diagnosis and prognosis.

scholarly journals Identification of the Key MicroRNAs and the miRNA-mRNA Regulatory Pathways in Prostate Cancer by Bioinformatics Methods

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Dongyang Li ◽  
Xuanyu Hao ◽  
Yongsheng Song
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Signaling Pathway ◽  
Regulatory Networks ◽  
Experimental Studies ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Tgf Beta ◽  
Regulatory Pathways ◽  
Ppi Networks

Objective. To identify key microRNAs (miRNAs) and their regulatory networks in prostate cancer.Methods. Four miRNA and three gene expression microarray datasets were downloaded for analysis from Gene Expression Omnibus database. The differentially expressed miRNA and genes were accessed by a GEO2R. Functional and pathway enrichment analyses were performed using the DAVID program. Protein-protein interaction (PPI) and miRNA-mRNA regulatory networks were constructed using the STRING and Cytoscape tool. Moreover, the results and clinical significance were validated in TCGA data.Results. We identified 26 significant DEMs, 633 upregulated DEGs, and 261 downregulated DEGs. Functional enrichment analysis indicated that significant DEGs were related to TGF-beta signaling pathway and TNF signaling pathway in PCa. Key DEGs such as HSPA8, PPP2R1A, CTNNB1, ADCY5, ANXA1, and COL9A2 were found as hub genes in PPI networks. TCGA data supported our results and the miRNAs were correlated with clinical stages and overall survival.Conclusions. We identified 26 miRNAs that may take part in key pathways like TGF-beta and TNF pathways in prostate cancer regulatory networks. MicroRNAs like miR-23b, miR-95, miR-143, and miR-183 can be utilized in assisting the diagnosis and prognosis of prostate cancer as biomarkers. Further experimental studies are required to validate our results.

scholarly journals Identification of Potentially Related Genes and Mechanisms Involved in Skeletal Muscle Atrophy Induced by Excessive Exercise in Zebrafish

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 761
Author(s):  
Chen-Chen Sun ◽  
Zuo-Qiong Zhou ◽  
Zhang-Lin Chen ◽  
Run-Kang Zhu ◽  
Dong Yang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Muscle Atrophy ◽  
Maximal Oxygen Consumption ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Skeletal Muscle Atrophy ◽  
Zebrafish Model ◽  
Excessive Exercise ◽  
Regulatory Pathways

Long-term imbalance between fatigue and recovery may eventually lead to muscle weakness or even atrophy. We previously reported that excessive exercise induces pathological cardiac hypertrophy. However, the effect of excessive exercise on the skeletal muscles remains unclear. In the present study, we successfully established an excessive-exercise-induced skeletal muscle atrophy zebrafish model, with decreased muscle fiber size, critical swimming speed, and maximal oxygen consumption. High-throughput RNA-seq analysis identified differentially expressed genes in the model system compared with control zebrafish. Gene ontology and KEGG enrichment analysis revealed that the upregulated genes were enriched in autophagy, homeostasis, circadian rhythm, response to oxidative stress, apoptosis, the p53 signaling pathway, and the FoxO signaling pathway. Protein–protein interaction network analysis identified several hub genes, including keap1b, per3, ulk1b, socs2, esrp1, bcl2l1, hsp70, igf2r, mdm2, rab18a, col1a1a, fn1a, ppih, tpx2, uba5, nhlrc2, mcm4, tac1, b3gat3, and ddost, that correlate with the pathogenesis of skeletal muscle atrophy induced by excessive exercise. The underlying regulatory pathways and muscle-pressure-response-related genes identified in the present study will provide valuable insights for prescribing safe and accurate exercise programs for athletes and the supervision and clinical treatment of muscle atrophy induced by excessive exercise.

Genome-Wide Identification of differently expressed lncRNAs, mRNAs, and circRNAs in patients with osteoarthritis

2020 ◽  
Vol 15 ◽  
Author(s):  
Yeqing Sun ◽  
Lei Chen ◽  
Yingqi Zhang ◽  
Jincheng Zhang ◽  
Shashi Ranjan Tiwari
Keyword(s):  
Regulatory Networks ◽  
Expression Profiles ◽  
Interleukin 1 ◽  
Interaction Network ◽  
Circular Rna ◽  
Negative Regulation ◽  
Differentially Expressed ◽  
Positive Regulation ◽  
Proteinprotein Interaction ◽  
Differently Expressed Genes

Background: Osteoarthritis (OA), one of the most important causes leading to joint disability, was considered as an untreatable disease. A series of genes were reported to regulate the pathogenesis of OA, including microRNAs, Long non-coding RNAs and Circular RNA. So far, the expression profiles and functions of lncRNAs, mRNAs, and circRNAs in OA are not fully understood. Objective: The present study aimed to identify differently expressed genes in OA. Methods: The present study conducted RNA-seq to identify differently expressed genes in OA. Ontology (GO) analysis was used to analysis the Molecular Function and Biological Process. KEGG pathway analysis was used to perform the differentially expressed lncRNAs in biological pathways. Results: Hierarchical clustering revealed a total of 943 mRNAs, 518 lncRNAs, and 300 circRNAs were dysregulated in OA compared to normal samples. Furthermore, we constructed differentially expressed mRNAs mediated proteinprotein interaction network, differentially expressed lncRNAs mediated trans regulatory networks, and competitive endogenous RNA (ceRNA) to reveal the interaction among these genes in OA. Bioinformatics analysis revealed these dysregulated genes were involved in regulating multiple biological processes, such as wound healing, negative regulation of ossification, sister chromatid cohesion, positive regulation of interleukin-1 alpha production, sodium ion transmembrane transport, positive regulation of cell migration, and negative regulation of inflammatory response. To the best of our knowledge, this study for the first time revealed the expression pattern of mRNAs, lncRNAs and circRNAs in OA. Conclusion: This study provided novel information to validate these differentially expressed RNAs may be as possible biomarkers and targets in OA.

Identification of key mRNAs and lncRNAs involved in the effects of anti-TWEAK on Osteosarcoma

2020 ◽  
Vol 15 ◽  
Author(s):  
Mingxuan Yang ◽  
Liangtao Zhao ◽  
Xuchang Hu ◽  
Haijun Feng ◽  
Xuewen Kang
Keyword(s):  
Dna Replication ◽  
Signaling Pathway ◽  
Bioinformatics Analysis ◽  
Mapk Signaling ◽  
Migration And Invasion ◽  
Type I ◽  
Interferon Signaling ◽  
Nf Kappa B ◽  
Ppi Networks ◽  
Coexpression Networks

Background: Osteosarcoma (OS) is one of the most common primary malignant bone tumors in teenagers. Emerging studies demonstrated TWEAK and Fn14 were involved in regulating cancer cell differentiation, proliferation, apoptosis, migration and invasion. Objective: The present study identified differently expressed mRNAs and lncRNAs after anti-TWEAK treatment in OS cells using GSE41828. Methods: We identified 922 up-regulated mRNAs, 863 downregulated mRNAs, 29 up-regulated lncRNAs, and 58 down-regulated lncRNAs after anti-TWEAK treatment in OS cells. By constructing PPI networks, we identified several key proteins involved in anti-TWEAK treatment in OS cells, including MYC, IL6, CD44, ITGAM, STAT1, CCL5, FN1, PTEN, SPP1, TOP2A, and NCAM1. By constructing lncRNAs coexpression networks, we identified several key lncRNAs, including LINC00623, LINC00944, PSMB8-AS1, LOC101929787. Result: Bioinformatics analysis revealed DEGs after anti-TWEAK treatment in OS were involved in regulating type I interferon signaling pathway, immune response related pathways, telomere organization, chromatin silencing at rDNA, and DNA replication. Bioinformatics analysis revealed differently expressed lncRNAs after antiTWEAK treatment in OS were related to telomere organization, protein heterotetramerization, DNA replication, response to hypoxia, TNF signaling pathway, PI3K-Akt signaling pathway, Focal adhesion, Apoptosis, NF-kappa B signaling pathway, MAPK signaling pathway, FoxO signaling pathway. Conclusion: : This study provided useful information for understanding the mechanisms of TWEAK underlying OS progression and identifying novel therapeutic markers for OS.

MAPK: A Key Player in the Development and Progression of Stroke

2020 ◽  
Vol 19 (4) ◽  
pp. 248-256
Author(s):  
Yangmin Zheng ◽  
Ziping Han ◽  
Haiping Zhao ◽  
Yumin Luo
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Complex Disease ◽  
Therapeutic Targets ◽  
Cell Types ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Effective Prevention ◽  
Prevention And Treatment ◽  
Different Cell Types

Conclusion: Stroke is a complex disease caused by genetic and environmental factors, and its etiological mechanism has not been fully clarified yet, which brings great challenges to its effective prevention and treatment. MAPK signaling pathway regulates gene expression of eukaryotic cells and basic cellular processes such as cell proliferation, differentiation, migration, metabolism and apoptosis, which are considered as therapeutic targets for many diseases. Up to now, mounting evidence has shown that MAPK signaling pathway is involved in the pathogenesis and development of ischemic stroke. However, the upstream kinase and downstream kinase of MAPK signaling pathway are complex and the influencing factors are numerous, the exact role of MAPK signaling pathway in the pathogenesis of ischemic stroke has not been fully elucidated. MAPK signaling molecules in different cell types in the brain respond variously after stroke injury, therefore, the present review article is committed to summarizing the pathological process of different cell types participating in stroke, discussed the mechanism of MAPK participating in stroke. We further elucidated that MAPK signaling pathway molecules can be used as therapeutic targets for stroke, thus promoting the prevention and treatment of stroke.

Transcriptional Control of Parturition: Insights from Gene Regulation Studies in the Myometrium

2021 ◽  
Author(s):  
Nawrah Khader ◽  
Virlana M Shchuka ◽  
Oksana Shynlova ◽  
Jennifer A Mitchell
Keyword(s):  
Transcription Factors ◽  
Regulatory Networks ◽  
Transcriptional Control ◽  
Progesterone Receptors ◽  
Activator Protein 1 ◽  
Transcriptional Regulatory Networks ◽  
Regulatory Pathways ◽  
Transcriptional Regulatory ◽  
Mechanistic Basis ◽  
Labour Onset

Abstract The onset of labour is a culmination of a series of highly coordinated and preparatory physiological events that take place throughout the gestational period. In order to produce the associated contractions needed for fetal delivery, smooth muscle cells in the muscular layer of the uterus (i.e. myometrium) undergo a transition from quiescent to contractile phenotypes. Here, we present the current understanding of the roles transcription factors play in critical labour-associated gene expression changes as part of the molecular mechanistic basis for this transition. Consideration is given to both transcription factors that have been well-studied in a myometrial context, i.e. activator protein 1 (AP-1), progesterone receptors (PRs), estrogen receptors (ERs), and nuclear factor kappa B (NF-κB), as well as additional transcription factors whose gestational event-driving contributions have been demonstrated more recently. These transcription factors may form pregnancy- and labour- associated transcriptional regulatory networks in the myometrium to modulate the timing of labour onset. A more thorough understanding of the transcription factor-mediated, labour-promoting regulatory pathways holds promise for the development of new therapeutic treatments that can be used for the prevention of preterm labour in at-risk women.

scholarly journals Identification of upregulated NF-κB inhibitor alpha and IRAK3 targeting lncRNA following intracranial aneurysm rupture-induced subarachnoid hemorrhage

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wei Leng ◽  
Dan Fan ◽  
Zhong Ren ◽  
Qiaoying Li
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Intracranial Aneurysm ◽  
Signaling Pathway ◽  
Aneurysm Rupture ◽  
Cytokine Receptor ◽  
Gene Set Enrichment Analysis ◽  
Receptor Interaction ◽  
Regulatory Pathways ◽  
Ruptured Intracranial Aneurysm ◽  
Neurotrophin Signaling

Abstract Background This study was performed to identify genes and lncRNAs involved in the pathogenesis of subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysm (RIA). Methods Microarray GSE36791 was downloaded from Gene Expression Omnibus (GEO) database followed by the identification of significantly different expressed RNAs (DERs, including lncRNA and mRNA) between patients with SAH and healthy individuals. Then, the functional analyses of DEmRNAs were conducted and weighted gene co-expression network analysis (WGCNA) was also performed to extract the modules associated with SAH. Following, the lncRNA-mRNA co-expression network was constructed and the gene set enrichment analysis (GSEA) was performed to screen key RNA biomarkers involved in the pathogenesis of SAH from RIA. We also verified the results in a bigger dataset GSE7337. Results Totally, 561 DERs, including 25 DElncRNAs and 536 DEmRNAs, were identified. Functional analysis revealed that the DEmRNAs were mainly associated with immune response-associated GO-BP terms and KEGG pathways. Moreover, there were 6 modules significantly positive-correlated with SAH. The lncRNA-mRNA co-expression network contained 2 lncRNAs (LINC00265 and LINC00937) and 169 mRNAs. The GSEA analysis showed that these two lncRNAs were associated with three pathways (cytokine-cytokine receptor interaction, neurotrophin signaling pathway, and apoptosis). Additionally, IRAK3 and NFKBIA involved in the neurotrophin signaling pathway and apoptosis while IL1R2, IL18RAP and IL18R1 was associated with cytokine-cytokine receptor interaction pathway. The expression levels of these genes have the same trend in GSE36791 and GSE7337. Conclusion LINC00265 and LINC00937 may be implicated with the pathogenesis of SAH from RIA. They were involved in three important regulatory pathways. 5 mRNAs played important roles in the three pathways.

scholarly journals Transcriptional landscape of cellular networks reveal interactions driving the dormancy mechanisms in cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dilara Uzuner ◽  
Yunus Akkoç ◽  
Nesibe Peker ◽  
Pınar Pir ◽  
Devrim Gözüaçık ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Regulatory Networks ◽  
Metastatic Cancer ◽  
Interaction Network ◽  
Current Treatment ◽  
Cellular Mechanisms ◽  
Protein Protein Interaction ◽  
Cancer Dormancy ◽  
Protein Protein Interaction Networks ◽  
First Time

AbstractPrimary cancer cells exert unique capacity to disseminate and nestle in distant organs. Once seeded in secondary sites, cancer cells may enter a dormant state, becoming resistant to current treatment approaches, and they remain silent until they reactivate and cause overt metastases. To illuminate the complex mechanisms of cancer dormancy, 10 transcriptomic datasets from the literature enabling 21 dormancy–cancer comparisons were mapped on protein–protein interaction networks and gene-regulatory networks to extract subnetworks that are enriched in significantly deregulated genes. The genes appearing in the subnetworks and significantly upregulated in dormancy with respect to proliferative state were scored and filtered across all comparisons, leading to a dormancy–interaction network for the first time in the literature, which includes 139 genes and 1974 interactions. The dormancy interaction network will contribute to the elucidation of cellular mechanisms orchestrating cancer dormancy, paving the way for improvements in the diagnosis and treatment of metastatic cancer.

scholarly journals The glycosyltransferase ST3GAL2 is regulated by miR-615-3p in the intestinal tract of Campylobacter jejuni infected mice

Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
De Xi ◽  
Lukas Hofmann ◽  
Thomas Alter ◽  
Ralf Einspanier ◽  
Stefan Bereswill ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Regulatory Networks ◽  
In Silico Analysis ◽  
Luciferase Reporter ◽  
Colonic Tissue ◽  
Tissue Samples ◽  
Vitro Model ◽  
Pathway Analyses

Abstract Background Campylobacter jejuni (C. jejuni) infections are of increasing importance worldwide. As a typical mucosal pathogen, the interaction of C. jejuni with mucins is a prominent step in the colonisation of mucosal surfaces. Despite recent advances in understanding the interaction between bacterial pathogens and host mucins, the mechanisms of mucin glycosylation during intestinal C. jejuni infection remain largely unclear. This prompted us to identify relevant regulatory networks that are concerted by miRNAs and could play a role in the mucin modification and interaction. Results We firstly used a human intestinal in vitro model, in which we observed altered transcription of MUC2 and TFF3 upon C. jejuni NCTC 11168 infection. Using a combined approach consisting of in silico analysis together with in vitro expression analysis, we identified the conserved miRNAs miR-125a-5p and miR-615-3p associated with MUC2 and TFF3. Further pathway analyses showed that both miRNAs appear to regulate glycosyltransferases, which are related to the KEGG pathway ‘Mucin type O-glycan biosynthesis’. To validate the proposed interactions, we applied an in vivo approach utilising a well-established secondary abiotic IL-10−/− mouse model for infection with C. jejuni 81-176. In colonic tissue samples, we confirmed infection-dependent aberrant transcription of MUC2 and TFF3. Moreover, two predicted glycosyltransferases, the sialyltransferases ST3GAL1 and ST3GAL2, exhibited inversely correlated transcriptional levels compared to the expression of the identified miRNAs miR-125a-5p and miR-615-3p, respectively. In this study, we mainly focused on the interaction between miR-615-3p and ST3GAL2 and were able to demonstrate their molecular interaction using luciferase reporter assays and RNAi. Detection of ST3GAL2 in murine colonic tissue by immunofluorescence demonstrated reduced intensity after C. jejuni 81-176 infection and was thus consistent with the observations made above. Conclusions We report here for the first time the regulation of glycosyltransferases by miRNAs during murine infection with C. jejuni 81-176. Our data suggest that mucin type O-glycan biosynthesis is concerted by the interplay of miRNAs and glycosyltransferases, which could determine the shape of intestinal glycosylated proteins during infection.

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