Differential expression of miR-4520a associated with gain-of-function mutations in Familial Mediterranean Fever (FMF)
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ABSTRACT:
ORGANISM(S): synthetic construct Homo sapiens
PROVIDER: GSE79954 | GEO | 2016/09/21
SECONDARY ACCESSION(S): PRJNA317491
REPOSITORIES: GEO
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Project description:microRNA analysis of PBMC from FMF patients vs healthy controls
2018-03-02 | GSE111311 | GEO
Project description:Familial Mediterranean fever (FMF) is an inflammatory genetic disease characterized by elevated systemic reactivity against commensal gut microbiota and high levels of gut Candida albicans. The current study investigated the effects of Lactobacillus acidophillus INMIA 9602 Er 317/402 strain (probiotic “Narine”) on the relative abundance of gut enteric bacteria, lactobacilli, Staphylococcus aureus, and Enteroccocus faecalis in Candida albicans-carrier and non-carrier FMF patients in remission with the main MEFV mutation patterns M694V/V726A- the prevalent MEFV gene mutation within FMF patients in the Armenian cohort. Our data revealed that M694V/V726A mutations in PURIN inflammasome leading to FMF disease brought to gender specific differences in microbial community structure in FMF patients. Possibly, long-term colchicine use suppresses the PURIN inflammasome/inhibits NLRP3 inflammasome-dependent IL-1β release influencing on overgrowth of C. albicans in gut microbiota of FMF patients. The comparison of Operational Taxonomic Units (OTUs) of enteric bacteria in C. albicans-carrier and non-carrier female patients revealed the statistically significant increase in OTUs of enterobacteria in C. albicans-carriers. In contrast to this, there were no differences in abundance of Enteroccocus faecalis between female FMF C. albicans-carriers compared with non-carriers, while male FMF C. albicans-carriers have increased abundance of E. faecalis in their gut microbiota compared with that of male patients with none carriers. The gut microbiota of FMF patients (both male and female) with C. albicans below baseline level contains high abundance of lactobacilli compared with C. albicans-carriers. The adoption of Lactobacillus acidophilus INMIA 9602 Er 317/402 leads to changes in gut microbiota composition of FMF patients. It reduces, in particularly, the abundance of enterobacteria in females, and Enteroccocus faecalis in men parallel with reducing the numbers of yeast in gut microbiota of FMF patients. We hypothesize that colchicine treatment changes the already-altered gut microbiota of FMF patients, thereby affecting the regulation of immune system by inhibition of NLRP3 inflammasome. Colchicine could lead to overgrowth of C. albicans in gut microbiota of FMF patients, whereas the Lactobacillus acidophilus INMIA 9602 Er 317/402 works on activation of inflammasome by new changes in gut microbiota of patients.
2018-03-16 | GSE111835 | GEO
Project description:Objective. Colchicine is an alkaloid that is used to alleviate acute gout and to prevent acute attacks of familial Mediterranean fever (FMF). However, it is not beneficial when given during the occurrence of an acute episode of FMF. It is believed that colchicine exerts its anti-inflammatory effect through direct interaction with microtubules. We aim to study the molecular basis of colchicine action by analysing the effect of this drug on global gene expression of HUVEC (human umbilical vein endothelial cell line) cells. Methods. HUVEC cells were exposed to various concentrations of colchicine and were harvested at different time points. Ribonucleic acid was extracted, amplified, reverse transcribed and hybridized to complementary deoxyribonucleic acid microarrrays containing more than 40,000 probes to human expressed sequence tags. This approach enabled us to have a global look at the transcriptional response induced by colchicine treatment. Results. Colchicine changed the expression of many genes in HUVEC cells following exposure to a concentration of 100 ng/ml or higher. Following short exposure (30 or 120 min), colchicine affected genes known to be involved in the cell cycle and its regulation. However, change in expression of genes involved in neutrophil migration or other inflammatory processes were observed mainly after 12 to 24 h. Conclusions. The anti-inflammatory effect of colchicine may be mediated not only through direct interaction with microtubules but also through changes at the transcriptional level. This latter effect apparently requires a higher concentration and a longer time to occur. This can explain the observation that colchicine does not have an immediate effect when given during an acute attack of FMF.
2005-10-07 | E-SMDB-3505 | biostudies-arrayexpress
Project description:Analysis of microRNAs in familial Mediterranean fever
| PRJNA436573 | ENA
Project description:Our data suggest that serum miR-204-3p has a potential as a useful biomarker among patients with FMF and that miR-204-3p plays a critical role as a suppressor to regulate the production of TLR4-related cytokines by targeting PI3K signaling pathway.
2017-06-01 | GSE98940 | GEO
Project description:The host response within the eschar of inoculation during Mediterranean spotted fever (MSF) has been poorly studied. Our objective was to evaluate the host response by comparing transcriptional profiles of eschars to controls using a whole-genome microarray. Hierarchical clustering revealed a signature of eschars consisting of 698 genes. The genes included in this signature were mainly up-regulated and were predominantly associated with immune response and signalling. New molecules involved notably in microbicidal and innate immunity response have also been found up-regulated in eschars such as MMP1, Defensin β4, the proinflammatory S100A9, and the T cell attracting CCL-18. Genes down-regulated were mainly associated with biological regulation. We also observed that eschars from severe cases of MSF displayed a specific signature with notably difference in degree of modulation compared to eschars from non severe MSF cases. Some parameters identified in this work should be tested as biomarkers for prognostic assessment in future studies. To evaluate the host response by comparing transcriptional profiles of eschars to controls
2012-12-07 | E-GEOD-32993 | biostudies-arrayexpress
Project description:The host response within the eschar of inoculation during Mediterranean spotted fever (MSF) has been poorly studied. Our objective was to evaluate the host response by comparing transcriptional profiles of eschars to controls using a whole-genome microarray. Hierarchical clustering revealed a signature of eschars consisting of 698 genes. The genes included in this signature were mainly up-regulated and were predominantly associated with immune response and signalling. New molecules involved notably in microbicidal and innate immunity response have also been found up-regulated in eschars such as MMP1, Defensin β4, the proinflammatory S100A9, and the T cell attracting CCL-18. Genes down-regulated were mainly associated with biological regulation. We also observed that eschars from severe cases of MSF displayed a specific signature with notably difference in degree of modulation compared to eschars from non severe MSF cases. Some parameters identified in this work should be tested as biomarkers for prognostic assessment in future studies.
2012-12-07 | GSE32993 | GEO
Project description:PFAPA, the syndrome of periodic fever associated with aphthous stomatitis, pharyngitis and/or cervical adenitis, is the most common periodic fever disease in children. Cases are mostly sporadic; the etiopathogenesis is unknown. In order to shed more insights into pathogenesis, we performed microarray expression analysis on samples from patients with PFAPA during and between flares, healthy controls and patients with hereditary autoinflammatory diseases during flares. RNA was extracted from whole peripheral blood from six patients with PFAPA syndrome during flares and asymptomatic intervals, six healthy controls and six patients with hereditary autoinflammatory diseases (2 familial Mediterranean fever (FMF), 1 TNF-receptor-asociated periodic fever syndrome (TRAPS) and 3 cryopyrin-associated periodic syndromes (CAPS)).
2011-06-20 | E-GEOD-17732 | biostudies-arrayexpress
Project description:Hereditary recurrent fevers (HRF) are a group of monogenic autoinflammatory diseases characterized by auto-resolving attacks of sterile inflammation caused by mutations of MEFV, TNFRSF1A and MVK genes1-3. Familial Mediterranean fever (FMF) is the prototype of a HPR and is caused by gain-of-function mutations of the MEFV gene, coding for pyrin4 5. Pyrin is part of the Pyrin-Inflammasome that controls the activation and secretion of interleukin (IL)-1β and can be activated by the cortical actin cytoskeleton remodeling induced by bacterial toxins via RhoA. Mevalonate kinase deficiency (MKD) is secondary to bi-allelic mutations of the gene coding for mevalonate kinase (MVK), an enzyme involved in the cholesterol biosynthesis. Loss-of-function MVK mutations lead to a defective sterol synthesis and to a reduced prenylation of small G proteins, such as RhoA, favoring the activation of the Pyrin-inflammasome6-8. TNF receptor-associated periodic syndrome (TRAPS) is secondary to autosomal dominant mutations of the gene coding for the type I receptor for TNF (TNFRSF1A), resulting in a heap of misfolded TNF receptor 1 in the endoplasmic reticulum, leading to oxidative stress, defective autophagy and consequent over-secretion of pro-inflammatory cytokines9 10. The clinical manifestations of HRFs are rather unspecific and consist mainly in fever, serositis, skin rash, limb and articular pain. No specific biomarkers able to distinguish one among the different HRFs have been identified, so far11. Moreover, the majority of the studies investigating the pathogenic consequences of the genes’ mutations associated with the three HRFs were focused on the few mechanisms classically associated to the pro-inflammatory activation of cells of the innate immunity (NF-kB and MAPK activation, IL-1b activation and secretion). Conversely, an unbiased analysis of possible additional intracellular pathways involved in the different conditions has not been exploited. Recently, large-scale proteomics based on high-resolution mass spectrometry (MS) has offered a systems-wide hypothesis-free method to analyze intracellular pathways in order to identify new disease biomarkers12-14. Here, we analyzed the proteomic signature of unstimulated and stimulated monocytes of patients with FMF, TRAPS and MKD, describing the dysregulated intracellular pathways associated with each condition for the identification of possible biomarkers and possible novel therapeutic targets.
2022-08-12 | PXD024068 | Pride
Project description:Diet can regulate gene and microRNA (miRNA) expression and various biological processes in the gut. Dietary interventions have been proposed as therapeutic approaches for several diseases, including cancer. In a pilot study, we showed that a low-inflammatory Mediterranean diet reduced markers of local and systemic inflammation in 27 patients with Familial Adenomatous Polyposis (FAP). We evaluated the changes induced by a low-inflammatory Mediterranean dietary intervention on fecal miRNome and intestinal tissue transcriptome in FAP subjects and assessed whether these changes could be associated with the beneficial effects observed in the pilot study. The diet modulated 41 fecal miRNAs, and this modulation remained for three months after the intervention. miR-5092-5p, miR-4527, and miR-3612-3p were positively correlated with adherence to the Mediterranean diet, while miR-6867-5p and miR-760-5p were negatively correlated with serum calprotectin levels. The altered miRNAs target genes mainly related to inflammatory pathways, DNA repair, metabolism, and cytoskeleton organization. Seventy genes were differentially expressed between adenoma and normal tissue. Most were different before the dietary intervention, but reached similar levels after the diet. Functional enrichment analysis identified the proinflammatory ERK1/2, cell cycle regulation and nutrient response pathways as commonly regulated by differentially expressed miRNAs and genes. These findings suggest that fecal miRNAs modulated by the diet reflect an epigenetic regulation occurring in tissues that seems to influence inflammatory pathways. miRNAs and genes with oncogenic and tumor suppressor functions are also regulated, highlighting the potential cancer-preventive effect of the low-inflammatory Mediterranean diet.
2024-01-12 | GSE218823 | GEO