Circulating miRNome profiling data in Behcet's syndrome.
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ABSTRACT:
SUBMITTER: Bagni G
PROVIDER: S-EPMC8488478 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Bone injury healing is an orchestrated process that starts with an inflammatory phase followed by repair and remodelling of the bone defect. The initial inflammation is characterized by local changes in immune cell populations and molecular mediators, including microRNAs (miRNAs). However, the systemic response to bone injury remains largely uncharacterized. Thus, this study aimed to profile the changes in the plasma miRnome after bone injury and determine its biological implications. Methods: A rat model of femoral bone defect was used, and animals were evaluated at days 3 and 14 after injury. Non-operated (NO) and sham operated animals were used as controls. Blood and spleen were collected and peripheral blood mononuclear cells (PBMC) and plasma were separated. Plasma miRnome was determined by RT-qPCR array and bioinformatics Ingenuity pathway analysis (IPA) was performed. Proliferation of bone marrow mesenchymal stem/stromal cells (MSC) was evaluated by Ki67 staining and high-throughput cell imaging. Candidate miRNAs were evaluated in splenocytes by RT-qPCR, and proteins found in the IPA analysis were analysed in splenocytes and PBMC by Western blot. Results: Bone injury resulted in timely controlled changes to the miRNA expression profile in plasma. At day 3 there was a major down-regulation of miRNA levels, which was partially recovered by day 14 post-injury. Interestingly, bone injury led to a significant up-regulation of let-7a, let-7d and miR-21 in plasma and splenocytes at day 14 relative to day 3 after bone injury, but not in sham operated animals. IPA predicted that most miRNAs temporally affected were involved in cellular development, proliferation and movement. MSC proliferation was analysed and found significantly increased in response to plasma of animals days 3 and 14 post-injury, but not from NO animals. Moreover, IPA predicted that miRNA processing proteins Ago2 and Dicer were specifically inhibited at day 3 post-injury, with Ago2 becoming activated at day 14. Protein levels of Ago2 and Dicer in splenocytes were increased at day 14 relative to day 3 post-bone injury and NO animals, while in PBMC, levels were reduced at day 3 (albeit Dicer was not significant) and remained low at day 14. Ephrin receptor B6 followed the same tendency as Ago2 and Dicer, while Smad2/3 was significantly decreased in splenocytes from day 14 relative to NO and day 3 post-bone injury animals. Conclusion: Results show a systemic miRNA response to bone injury that is regulated in time and is related to inflammation resolution and the start of bone repair/regeneration, unravelling candidate miRNAs to be used as biomarkers in the monitoring of healthy bone healing and as therapeutic targets for the development of improved bone regeneration therapies.
| S-EPMC6071520 | biostudies-literature
Project description:Circulating plasma miRNAs profiling in platelets-free plasma samples from Behçet's disease patients compared with healthy subjects, aimed to both pathogenesis elucidation and candidate non-invasive biomarkers identification.
2020-04-01 | GSE145191 | GEO
Project description:Behçet's disease (BD) is a chronic, relapsing, multisystemic inflammatory disorder with unanswered questions regarding its etiology/pathogenesis and classification. Distinct manifestation based subsets, pronounced geographical variations in expression, and discrepant immunological abnormalities raised the question whether Behçet's is "a disease or a syndrome". To answer the preceding question we aimed to display and compare the molecular mechanisms underlying distinct subsets of BD. For this purpose, the expression data of the gene expression profiling and association study on BD by Xavier et al (2013) was retrieved from GEO database and reanalysed by gene expression data analysis/visualization and bioinformatics enrichment tools. There were 15 BD patients (B) and 14 controls (C). Three subsets of BD patients were generated: MB (isolated mucocutaneous manifestations, n = 7), OB (ocular involvement, n = 4), and VB (large vein thrombosis, n = 4). Class comparison analyses yielded the following numbers of differentially expressed genes (DEGs); B vs C: 4, MB vs C: 5, OB vs C: 151, VB vs C: 274, MB vs OB: 215, MB vs VB: 760, OB vs VB: 984. Venn diagram analysis showed that there were no common DEGs in the intersection "MB vs C" ? "OB vs C" ? "VB vs C". Cluster analyses successfully clustered distinct expressions of BD. During gene ontology term enrichment analyses, categories with relevance to IL-8 production (MB vs C) and immune response to microorganisms (OB vs C) were differentially enriched. Distinct subsets of BD display distinct expression profiles and different disease associated pathways. Based on these clear discrepancies, the designation as "Behçet's syndrome" (BS) should be encouraged and future research should take into consideration the immunogenetic heterogeneity of BS subsets. Four gene groups, namely, negative regulators of inflammation (CD69, CLEC12A, CLEC12B, TNFAIP3), neutrophil granule proteins (LTF, OLFM4, AZU1, MMP8, DEFA4, CAMP), antigen processing and presentation proteins (CTSS, ERAP1), and regulators of immune response (LGALS2, BCL10, ITCH, CEACAM8, CD36, IL8, CCL4, EREG, NFKBIZ, CCR2, CD180, KLRC4, NFAT5) appear to be instrumental in BS immunopathogenesis.
| S-EPMC4758705 | biostudies-literature
Project description:BackgroundMoyamoya disease (MMD) is characterized by progressive stenosis of intracranial arteries in the circle of Willis with unknown etiology even after the identification of a Moyamoya susceptible gene, RNF213. Recently, differences in epigenetic regulations have been investigated by a case-control study in MMD. Here, we employed a disease discordant monozygotic twin-based study design to unmask potential confounders.MethodsCirculating genome-wide microRNA (miRNome) profiling was performed in MMD-discordant monozygotic twins, non-twin-MMD patients, and non-MMD healthy volunteers by microarray followed by qPCRvalidation, using blood samples. Differential plasma-microRNAs were further quantified in endothelial cells differentiated from iPS cell lines (iPSECs) derived from another independent non-twin cohort. Lastly, their target gene expression in the iPSECs was analyzed.ResultsMicroarray detected 309 plasma-microRNAs in MMD-discordant monozygotic twins that were also detected in the non-twin cohort. Principal component analysis of the plasma-microRNA expression level demonstrated distinct 2 groups separated by MMD and healthy control in the twin- and non-twin cohorts. Of these, differential upregulations of hsa-miR-6722-3p/- 328-3p were validated in the plasma of MMD (absolute log2 expression fold change (logFC) > 0.26 for the twin cohort; absolute logFC > 0.26, p < 0.05, and q < 0.15 for the non-twin cohort). In MMD derived iPSECs, hsa-miR-6722-3p/- 328-3p showed a trend of up-regulation with a 3.0- or higher expression fold change. Bioinformatics analysis revealed that 41 target genes of miR-6722-3p/- 328-3p were significantly down-regulated in MMD derived iPSECs and were involved in STAT3, IGF-1-, and PTEN-signaling, suggesting a potential microRNA-gene expression interaction between circulating plasma and endothelial cells.ConclusionsOur MMD-discordant monozygotic twin-based study confirmed a novel circulating microRNA signature in MMD as a potential diagnostic biomarker minimally confounded by genetic heterogeneity. The novel circulating microRNA signature can contribute for the future functional microRNA analysis to find new diagnostic and therapeutic target of MMD.
| S-EPMC6114494 | biostudies-literature
Project description:Clustering is an important clinical feature of Behçet's syndrome (BS) and may have pathogenetic and therapeutic implications. Recent and previous studies on BS phenotype differ substantially in terms of methodology. Correlation matrices and factor analyses were not efficient enough to uncover clusters. Clustering patterns may change according to demographic factors such as age and sex. Clustering patterns may also be profoundly influenced by the misperception of symptoms that are assumed to be secondary to BS, when, in fact, they represent manifestations of BD mimics. This can give rise to misleading conclusions and should be kept in mind when interpreting data obtained by clustering or other phenotype analyses of BS. A true geographical/racial variability in disease expression could be studied in a multinational consensus cohort. Pathogenetic studies in separate clusters of BS have still been lacking.
| S-EPMC9617315 | biostudies-literature
Project description:Circulating miRNome expression profiling in Behçet's disease
| PRJNA606280 | ENA
Project description:Frailty is an aging-related pathology, defined as a state of increased vulnerability to stressors, leading to a limited capacity to meet homeostatic demands. Extracellular microRNAs (miRNAs) were proposed as potential biomarkers of various disease conditions, including age-related pathologies. The primary objective of this study was to identify blood miRNAs that could serve as potential biomarkers and candidate mechanisms of frailty. Using the Fried index, we enrolled 22 robust and 19 frail subjects. Blood and urine samples were analysed for several biochemical parameters. We observed that sTNF-R was robustly upregulated in the frail group, indicating the presence of an inflammatory state. Further, by RNA-seq, we profiled 2654 mature miRNAs in the whole blood of the two groups. Expression levels of selected differentially expressed miRNAs were validated by qPCR, and target prediction analyses were performed for the dysregulated miRNAs. We identified 2 miRNAs able to significantly differentiate frail patients from robust subjects. Both miR-101-3p and miR-142-5p were found to be downregulated in the frail vs. robust group. Finally, using bioinformatics targets prediction tools, we explored the potential molecular mechanisms and cellular pathways regulated by the two miRNAs and potentially involved in frailty.
| S-EPMC8872439 | biostudies-literature
Project description:Background:Behçet's disease (BD) is a chronic inflammatory multisystem disease characterized by oral and genital ulcers, uveitis, and skin lesions. MicroRNAs (miRNAs) are key regulators of immune responses. Differential expression of miRNAs has been reported in several inflammatory autoimmune diseases; however, their role in BD is not fully elucidated. We aimed to identify miRNA expression signatures associated with BD and to investigate their potential implication in the disease pathogenesis. Methods:miRNA microarray analysis was performed in blood cells of BD patients and healthy controls. miRNA expression profiles were analyzed using Affymetrix arrays with a comprehensive coverage of miRNA sequences. Pathway analyses were performed, and the global miRNA profiling was combined with transcriptoma data in BD. Deregulation of selected miRNAs was validated by real-time PCR. Results:We identified specific miRNA signatures associated with BD patients with active disease. These miRNAs target pathways relevant in BD, such as TNF, IFN gamma, and VEGF-VEGFR signaling cascades. Network analysis revealed several miRNAs regulating highly connected genes within the BD transcriptoma. Conclusions:The combined analysis of deregulated miRNAs and BD transcriptome sheds light on some epigenetic aspects of BD identifying specific miRNAs, which may represent promising candidates as biomarkers and/or for the design of novel therapeutic strategies in BD.
| S-EPMC5964440 | biostudies-literature
Project description:Behçet's syndrome (BS) is a multisystem vasculitis that presents with a variety of mucocutaneous manifestations such as oral and genital ulcers, papulopustular lesions and erythema nodosum as well as ocular, vascular, gastrointestinal and nervous system involvement. Although it occurs worldwide, it is especially prevalent in the Far East and around the Mediterranean Sea. Male gender and younger age at disease onset are associated with a more severe disease course. The management of BS depends on the severity of symptoms. If untreated, morbidity and mortality are considerably high in patients with major organ involvement. Multidisciplinary patient care is essential for the management of BS, as it is for other multisystem diseases. Rheumatologists, dermatologists, ophthalmologists, neurologists, cardiovascular surgeons and gastroenterologists are members of the multidisciplinary team. In this study, we reviewed the epidemiology, etiology, diagnostic criteria sets, clinical findings and treatment of BS and highlighted the importance of the multidisciplinary team in the management of BS.
| S-EPMC5565245 | biostudies-other
Project description:Post-surgical management is an important issue in veterinary medicine, requiring biomarkers with high sensitivity and specificity for timely and effective treatment. Emerging evidence suggests that miRNAs are promising stress- and pain-related markers. The aims were to profile the circulating miRNA signature in plasma of turtles (Trachemys scripta) and point out potential candidate biomarkers to assess the status of the animal. The plasma of female turtles underwent surgical gonadectomy were collected 24 h pre-surgery, and 2.5 h and 36 h post-surgery. The expression of miRNAs was profiled by Next Generation Sequencing and the dysregulated miRNAs were validated using RT-qPCR. The diagnostic value of miRNAs was calculated by ROC curves. The results showed that 14 miRNAs were differentially expressed over time. RT-qPCR validation highlighted that 2-miR-499-3p and miR-203-5p-out of 8 miRNAs tested were effectively modulated. The Area Under the Curve (AUC) of miR-203-5p was fair (AUC 0.7934) in discriminating pre- and 36 h post-surgery samples and poor for other time points; the AUC of miR-499-3p was excellent (AUC 0.944) in discriminating pre-surgery and 2.5 h post-surgery samples, and fair in discriminating pre-surgery and 36 h post-surgery (AUC 0.7292) and 2.5 h and 36 h post-surgery (AUC 0.7569) samples. In conclusion, we demonstrated for the first time that miRNAs profile changes in plasma of turtles underwent surgical oophorectomy and identified miR-203-5p and miR-499-3p as potential candidate biomarkers to assess animals' status. Further studies are necessary to confirm their diagnostic value and to investigate functional and mechanistic networks to improve our understanding of the biological processes.
| S-EPMC8289937 | biostudies-literature