A5041354033- Protease and Inhibitor Mechanisms
- Cell Adhesion Molecules Research
- Adipokines, Inflammation, and Metabolic Diseases
- Blood Coagulation and Thrombosis Mechanisms
- Platelet Disorders and Treatments
- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- Atherosclerosis and Cardiovascular Diseases
- Signaling Pathways in Disease
- Protein Kinase Regulation and GTPase Signaling
- Lipoproteins and Cardiovascular Health
- Cellular transport and secretion
- HER2/EGFR in Cancer Research
- PI3K/AKT/mTOR signaling in cancer
- Ubiquitin and proteasome pathways
- Liver Disease Diagnosis and Treatment
- Immune Response and Inflammation
- Blood properties and coagulation
- Diabetes and associated disorders
- RNA and protein synthesis mechanisms
- Hereditary Neurological Disorders
- Photoreceptor and optogenetics research
- Endoplasmic Reticulum Stress and Disease
- Photochromic and Fluorescence Chemistry
Aix-Marseille Université
2014-2024
Unité de recherche sur les maladies cardiovasculaires et métaboliques
2018-2024
Inserm
2013-2023
Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
2020-2023
Nutrition, Obésité et Risque Thrombotique
2012-2017
Société Française de Médecine Vasculaire
2011-2017
Institut National de la Recherche Agronomique du Niger
2015
Bipar
2014
Institut de Neurobiologie de la Méditerranée
2000-2011
Hôpital de la Timone
2004
Plasminogen activator inhibitor type 1 (PAI-1) contributes to the pathogenesis of atherothrombosis. Its plasma level is strongly correlated with parameters that define insulin resistance syndrome, in particular BMI and visceral accumulation body fat, suggesting PAI-1 may be an adipose tissue–derived circulating peptide. The present study was designed investigate expression by human tissue its different cellular fractions. Special interest has been paid amount antigen produced omental versus...
Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that has demonstrated cardiovascular and renal protection in patients with type diabetes (T2D). We hypothesized empaglifozin (EMPA) could modulate ectopic fat stores myocardial energetics high-fat-high-sucrose (HFHS) diet mice diabetics
The nature of an inherited platelet disorder was investigated in three siblings affected by severe bleeding. Using whole-exome sequencing, we identified the culprit mutation (cG742T) RAS guanyl-releasing protein-2 (RASGRP2) gene coding for calcium- and DAG-regulated guanine exchange factor-1 (CalDAG-GEFI). Platelets from individuals carrying present a reduced ability to activate Rap1 perform proper αIIbβ3 integrin inside-out signaling. Expression CalDAG-GEFI mutant HEK293T cells abolished...
Variants in ETV6, which encodes a transcription repressor of the E26 transformation-specific family, have recently been reported to be responsible for inherited thrombocytopenia and hematologic malignancy. We sequenced DNA from cases with unexplained dominant identified six likely pathogenic variants five are novel. observed low repressive activity all tested ETV6 variants, located binding domain (encoding p.A377T, p.Y401N) led reduced corepressors. also large expansion megakaryocyte...
Vitamin D (VD) displays immunoregulatory effects and reduces adipocyte inflammation, which may participate to a reduction of adipose tissue macrophage infiltration in the context obesity-associated low-grade inflammation. These observations have been described mainly vitro, through evaluation limited number inflammatory markers. Here, we studied 1,25 dihydroxy-VD on chemokine network expression adipocytes (by transcriptomic approach), confirm physiological relevance these data vivo, by...
PPAR antagonists are ligands that bind their receptor with high affinity without transactivation activity. Recently, they have been demonstrated to maintain insulin-sensitizing and antidiabetic properties, serve as an alternative treatment for metabolic diseases. In this work, affinity-based bioassay was found be effective selecting from the dried extract of African plant (Diospyros bipindensis). Among ligands, we identified betulinic acid (BA), a compound already known its...
Insulin receptor (IR) plays a key role in the control of glucose homeostasis; however, regulation its cellular expression remains poorly understood. Here we show that amount biologically active IR is regulated by cleavage ectodomain, β-site amyloid precursor protein cleaving enzyme 1 (BACE1), concentration-dependent manner. In vivo studies demonstrate BACE1 regulates and insulin signaling liver. During diabetes, BACE1-dependent increased liver reduced, whereas infusion inhibitor partially...
Migration and proliferation of arterial smooth muscle cells (SMCs) play a prominent role in the development atherosclerotic plaques restenosis lesions. Most growth-regulatory molecules potentially involved these pathological conditions also demonstrate chemotactic properties. Extracellular purine pyrimidine nucleotides have been shown to induce cell cycle progression elicit growth cultured vascular SMCs. Moreover, P2Y 2 ATP/UTP receptor was overexpressed intimal thickening, suggesting...
Plasminogen activator inhibitor 1 (PAI-1) is likely to play a role in vascular disease, primarily subjects with android obesity. It has been demonstrated that PAI-1 overexpressed adipose tissue from obese and visceral produced more than subcutaneous fat. In the present study, effect of insulin glucocorticoids, which are key mediators metabolism, was examined relation synthesis by human explants (HAT), collagenase isolated adipocytes (IHA), cultured stromal cells (cSC), differentiated murine...
Abstract Serine proteases are now considered as crucial contributors to the development of human colon cancer. We have shown recently that thrombin is a potent growth factor for cancer cells through activation aberrantly expressed protease-activated receptor 1 (PAR1). Here, we analyzed signaling pathways downstream PAR1 activation, which lead cell proliferation in HT-29 cells. Our data consistent with following cascade events on by or specific activating peptide: (a) matrix...
Abstract The main function of plasminogen activator inhibitor type 1 (PAI-1) is to decrease fibrinolysis, which leads fibrin accumulation. An elevated plasma PAI-1 concentration has been identified as a risk factor for the development myocardial infarction, and an association between polymorphism promoter levels described. Our aim was identify new polymorphisms in gene further examine relationship genotypes circulating levels. We report presence 4 that were by nonisotopic single-strand...
FcγRIIIA/CD16A, the low-affinity receptor for IgG Fc portion expressed on human CD56(dim) NK cells and involved in Ab-dependent cell cytotoxicity, is shed upon activation. We found that recombinant a disintegrin metalloprotease (ADAM) 17 cleaved ectodomain of FcγRIIIA/CD16A peptide which sequence encompasses aa 191-201 stalk region but not ADAM10. MALDI-TOF analysis revealed was between Ala(195) Val(196) (i.e., 1 upstream expected position). This location cleavage site confirmed by finding...
A new series of derivatives the PPARα/γ dual agonist 1 allowed us to identify ligand (S)-6 as a potent partial both PPARα and γ subtypes. X-ray studies in PPARγ revealed two different binding modes canonical site. However, was also able bind an alternative site demonstrated by transactivation assay presence antagonist supported from docking experiments. This compound did not activate PPARγ-dependent program adipocyte differentiation inducing very less severe lipid accumulation compared...
Matrix metalloproteinase activity is essential for proper extracellular matrix remodeling that takes place during adipose tissue formation. Four inhibitors of metalloproteinases (TIMPs) regulate their activity. However, the role TIMPs in adipocyte differentiation poorly understood. We found expression all was modified differentiation, but TIMP-3 distinguished by its extreme down-regulation. closely linked to process. Indeed, it remained low increased when cell prevented. identified...