A5001517455- Rheumatoid Arthritis Research and Therapies
- NF-κB Signaling Pathways
- Spondyloarthritis Studies and Treatments
- Cytokine Signaling Pathways and Interactions
- Psoriasis: Treatment and Pathogenesis
- Spine and Intervertebral Disc Pathology
- MicroRNA in disease regulation
- Chronic Lymphocytic Leukemia Research
- Cancer-related molecular mechanisms research
- Signaling Pathways in Disease
- Dermatology and Skin Diseases
- Systemic Lupus Erythematosus Research
- Peptidase Inhibition and Analysis
- interferon and immune responses
- Immune Response and Inflammation
- Circular RNAs in diseases
- Osteoarthritis Treatment and Mechanisms
- Chronic Myeloid Leukemia Treatments
- Quinazolinone synthesis and applications
- Diet and metabolism studies
- Atherosclerosis and Cardiovascular Diseases
- RNA Research and Splicing
- Virus-based gene therapy research
- Helicobacter pylori-related gastroenterology studies
- Ubiquitin and proteasome pathways
Alexander Fleming Biomedical Sciences Research Center
2004-2023
National and Kapodistrian University of Athens
2017
University of Zurich
2012
Inserm
2004
Institut Necker Enfants Malades
2004
National Hellenic Research Foundation
1994
<h3>Objective</h3> To identify novel microRNA (miR) associations in synovial fibroblasts (SF), by performing miR expression profiling on cells isolated from the human tumour necrosis factor (TNF) transgenic mouse model (TghuTNF, Tg197) and patients biopsies. <h3>Methods</h3> SF TghuTNF wild-type (WT) control mice were determined deep sequencing (miR-seq) arthritic profile was established pairwise comparisons. Quantitative PCR analysis utilised for validation, gene quantitation patient SF....
Tumor progression locus-2 (Tpl2) kinase is a major inflammatory mediator in immune cell types recently found to be genetically associated with bowel diseases (IBDs). Here we show that Tpl2 may exert dominant homeostatic rather than function the intestine mediated specifically by subepithelial intestinal myofibroblasts (IMFs). Mice complete or IMF-specific ablation are highly susceptible epithelial injury-induced colitis showing impaired compensatory proliferation crypts and extensive...
TNF has remarkable antitumor activities; however, therapeutic applications have not been possible because of the systemic and lethal proinflammatory effects induced by TNF. Both inflammatory are mediated receptor p55 (p55TNFR) (encoded Tnfrsf1a gene). The effect stems from an induction cell death in tumor endothelium, but type that initiates cascade unclear. Using conditional knockout or reactivation mice, we found expression level p55TNFR intestinal epithelial cells (IECs) is a crucial...
Rheumatoid arthritis is a progressive, highly debilitating disease where early diagnosis, enabling rapid clinical intervention, would provide obvious benefits to patients, healthcare systems, and society. Novel biomarkers that enable noninvasive diagnosis of the onset progression one route achieving this goal. Here metabolic profiling method has been applied investigate development in Tg197 mouse model. Hind limb extract demonstrated clear differences phenotypes between control (wild type)...
Abstract Fibroblasts are key regulators of inflammation, fibrosis, and cancer. Targeting their activation in these complex diseases has emerged as a novel strategy to restore tissue homeostasis. Here, we present multidisciplinary lead discovery approach identify optimize small molecule inhibitors pathogenic fibroblast activation. The study encompasses medicinal chemistry, molecular phenotyping assays, chemoproteomics, bulk RNA‐sequencing analysis, target validation experiments, chemical...
<h3>Objectives</h3> Patients with rheumatoid arthritis and spondyloarthritisshow higher mortality rates, mainly caused by cardiac comorbidities. The TghuTNF (Tg197) model develops tumour necrosis factor (TNF)-driven mesenchymalsynovial fibroblast (SF)-dependent polyarthritis. Here, we investigate whether this develops, similarly to human patients, comorbid heart pathology explore cellular molecular mechanisms linking <h3>Methods</h3> Histopathological analysis echocardiographic evaluation of...
Abstract Aims Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting joints and blood vessels. Despite low levels of low-density lipoprotein cholesterol (LDL-C), RA patients exhibit endothelial dysfunction are at increased risk death from cardiovascular complications, but the molecular mechanism action unknown. We aimed in present study to identify mouse model with RA. Methods results Endothelium-dependent relaxations acetylcholine were reduced aortae two tumour necrosis...
Synovial fibroblasts (SFs) are key pathogenic drivers in rheumatoid arthritis (RA). Their vivo activation by TNF is sufficient to orchestrate full arthritic pathogenesis animal models, and blockade proved efficacious for a high percentage of patients with RA albeit coinducing rare but serious side effects. Aiming find new potent therapeutics, we applied the L1000CDS2 search engine, repurpose drugs that could reverse expression signature arthritogenic human TNF-transgenic (hTNFtg) SFs. We...
Mesenchymal TNF signaling is etiopathogenic for inflammatory diseases such as rheumatoid arthritis and spondyloarthritis (SpA). The role of Tnfr1 in has been documented; however, Tnfr2 functions are unknown. Here, we investigate the mesenchymal-specific TnfΔARE mouse model SpA heart valve stenosis comorbidity by cell-specific, Col6a1-cre-driven gene targeting. We find that TNF/Tnfr2 resident synovial fibroblasts (SFs) valvular interstitial cells (VICs) detrimental both pathologies, pointing...
TGFβ-activated kinase 1 (TAK1), a member of the mitogen-activated protein (MAP3K) family, is considered key intermediate in multitude innate immune signaling pathways. Yet, specific role TAK1 myeloid compartment during inflammatory challenges has not been revealed. To address this question, we generated myeloid-specific kinase-dead mutant mice. deficiency macrophages results impaired NF-κB and JNK activation upon stimulation with lipopolysaccharide (LPS). Moreover, TAK1-deficient neutrophils...
Abstract Background The transmembrane-TNF transgenic mouse, TgA86, has been shown to develop spontaneously peripheral arthritis with signs of axial involvement. To assess similarity human spondyloarthritis, we performed detailed characterization the axial, peripheral, and comorbid pathologies this model. Methods TgA86 bone were assessed at different ages using CT imaging spine, tail vertebrae, hind limbs characterized in detail by histopathological immunohistochemical analysis. Cardiac...
Anti-TNF agents have been in the first line of treatment various inflammatory diseases such as Rheumatoid Arthritis and Crohn's Disease, with a number different biologics being currently use. A detailed analysis their effect at transcriptome level has nevertheless lacking. We herein present concise an extended transcriptomics profiling four anti-TNF upon established hTNFTg (Tg197) mouse model spontaneous polyarthritis. implement series computational analyses that include clustering...
miRNAs constitute fine-tuners of gene expression and are implicated in a variety diseases spanning from inflammation to cancer. miRNA is deregulated rheumatoid arthritis (RA); however, their specific role key arthritogenic cells such as the synovial fibroblast (SF) remains elusive. Previous studies have shown that Mir221/222 upregulated RA SFs. Here, we demonstrate TNF IL-1β but not IFN-γ activated Mir221 /222 murine SF-specific overexpression huTNFtg mice led further expansion SFs disease...
Children with chronic inflammation are often treated glucocorticoids (GCs) and many of them experience growth retardation. It is poorly understood how GCs interact inflammatory cytokines causing failure as earlier experimental studies have been performed in healthy animals. To address this gap knowledge, we used a transgenic mouse model where human TNF overexpressed (huTNFTg) leading to polyarthritis starting from the first week age. Our results showed that femur bone length plate height...
Abstract Background Genetic modification of embryonic stem (ES) cells represents a powerful tool for transgenic and developmental experiments. We report that retroviral constructs based on murine embryonal cell virus (MESV) can efficiently deliver express Cre recombinase or post‐translationally inducible Cre‐Progesterone receptor (Cre.PR) fusion in mouse fibroblasts ES cells. Methods To study the vectors sensitive reporter line, 3TZ, was derived from 3T6 fibroblast line expresses...
Filensin and phakinin are two lens‐specific members of the intermediate filament (IF) superfamily proteins. They coassemble to form a beaded submembraneous filamentous network, filaments (BFs). The low sequence homology differences in assembly compared other IF proteins do not allow their classification any five subgroups. organization gene exon/intron boundaries provides evidence that this partner may be sharing common origin with type I cytokeratin genes. Here we report molecular cloning,...
Abstract Background New medications for Rheumatoid Arthritis (RA) have emerged in the last decades, including Disease Modifying Antirheumatic Drugs (DMARDs) and biologics. However, there is no known cure, since a significant proportion of patients remain or become non-responders to current therapies. The development new mode-of-action treatment schemes involving combination therapies could prove successful greater number RA patients. Methods We investigated effect Tyrosine Kinase inhibitors...
Abstract Fibroblasts are key regulators of inflammation, fibrosis, and cancer. Targeting their activation in these complex diseases has emerged as a novel strategy to restore tissue homeostasis. Here, we present multidisciplinary lead discovery approach identify optimize small molecule inhibitors pathogenic fibroblast activation. The study encompasses medicinal chemistry, molecular phenotyping assays, chemoproteomics, bulk RNA‐sequencing analysis, target validation experiments, chemical...
Interleukin-23 (IL-23) is a crucial cytokine implicated in chronic inflammation and autoimmunity, associated with various diseases such as psoriasis, psoriatic arthritis, systemic lupus erythematosus (SLE). This study aimed to create characterize transgenic mouse model overexpressing human IL-23A (TghIL-23A), providing valuable tool for investigating the pathogenic role of evaluating efficacy anti-human therapeutics.