A5089694873- Drug Transport and Resistance Mechanisms
- Drug-Induced Hepatotoxicity and Protection
- Cancer, Hypoxia, and Metabolism
- Liver Diseases and Immunity
- Pharmacological Effects and Toxicity Studies
- Galectins and Cancer Biology
- Glioma Diagnosis and Treatment
- Liver Disease Diagnosis and Treatment
- Pharmacogenetics and Drug Metabolism
- Mitochondrial Function and Pathology
- Glycosylation and Glycoproteins Research
- Pediatric Hepatobiliary Diseases and Treatments
- Cancer Research and Treatments
- Drug Solubulity and Delivery Systems
- Epigenetics and DNA Methylation
- Hepatitis B Virus Studies
- Muscle Physiology and Disorders
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- interferon and immune responses
- Immune cells in cancer
- RNA Interference and Gene Delivery
- Protein Kinase Regulation and GTPase Signaling
- 3D Printing in Biomedical Research
- Advanced Proteomics Techniques and Applications
Bordeaux Population Health
2023-2025
Inserm
2013-2025
Université de Bordeaux
2024-2025
Jewish General Hospital
2019-2024
McGill University
2019-2024
uOttawa Brain and Mind Research Institute
2022-2024
University of Ottawa
2022-2024
Université de Rennes
2013-2019
Centre Hospitalier Universitaire de Rennes
2019
Foie, Métabolisme, Cancer
2013-2019
Abstract Intrahepatic cholestasis represents a frequent manifestation of drug-induced liver injury; however, the mechanisms underlying such injuries are poorly understood. In this study human HepaRG and primary hepatocytes, we found that bile canaliculi (BC) underwent spontaneous contractions, which essential for acid (BA) efflux require alternations in myosin light chain (MLC2) phosphorylation/dephosphorylation. Short exposure to 6 cholestatic compounds revealed BC constriction dilation...
The role of hepatobiliary transporters in drug-induced liver injury remains poorly understood. Various vivo and vitro biological approaches are currently used for studying hepatic transporters; however, appropriate localization functional activity these essential normal biliary flow drug transport. Human hepatocytes (HHs) considered as the most suitable cell model but erratic availability inter-donor variations limit their use. In this work, we aimed to compare influx efflux differentiated...
Glioblastoma contains a rare population of self-renewing brain tumor stem cells (BTSCs) which are endowed with properties to proliferate, spur the growth new tumors, and at same time, evade ionizing radiation (IR) chemotherapy. However, drivers BTSC resistance therapy remain unknown. The cytokine receptor for oncostatin M (OSMR) regulates proliferation glioblastoma tumorigenesis. Here, we report our discovery mitochondrial OSMR that confers IR via regulation oxidative phosphorylation,...
Abstract The function and maintenance of muscle stem cells (Mu SC s) are tightly regulated by signals originating from their niche environment. Skeletal myofibers a principle component the Mu in direct contact with cells. Here, we show that Myf6 establishes ligand/receptor interaction between associated fibers. Our data transcriptionally regulates broad spectrum myokines muscle‐secreted proteins skeletal myofibers, including EGF . EGFR signaling blocks p38 MAP kinase‐induced differentiation...
Mechanisms involved in drug-induced cholestasis humans remain poorly understood. Although cyclosporine A (CsA) and tacrolimus (FK506) share similar immunosuppressive properties, only CsA is known to cause dose-dependent cholestasis. Here, we have investigated the mechanisms implicated early cholestatic effects of using differentiated human HepaRG cell line. Inhibition efflux uptake taurocholate was evidenced as 15 min 1 h respectively after addition 10μM CsA; it peaked at around 2...
Alteration of bile acid (BA) profiles and secretion by cholestatic drugs represents a major clinical issue. Species differences exist in BA composition, synthesis, regulation; however presently, there is no vitro reproducible cell model to perform studies on BAs humans. We have evaluated the capacity human HepaRG line synthesize, conjugate, secrete BAs, analyzed changes content profile after cyclosporine A (CsA) treatment. Our data show that cells produced normal at daily levels comparable,...
Intrahepatic cholestasis represents 20%–40% of drug-induced injuries from which a large proportion remains unpredictable. We aimed to investigate mechanisms underlying and improve its early detection using human HepaRG cells set 12 cholestatic drugs six noncholestatic drugs. In this study, we analyzed bile canaliculi dynamics, Rho kinase (ROCK)/myosin light chain (MLCK) pathway implication, efflux inhibition taurocholate [a predominant salt export pump (BSEP) substrate], expression the major...
Brain tumor stem cells (BTSCs) and intratumoral heterogeneity represent major challenges in glioblastoma therapy. Here, we report that the LGALS1 gene, encoding carbohydrate binding protein, galectin1, is a key regulator of BTSCs resistance to Genetic deletion alters BTSC gene expression profiles results downregulation sets associated with mesenchymal subtype glioblastoma. Using combination pharmacological genetic approaches, establish inhibition signaling impairs self-renewal, suppresses...
Several factors are thought to be implicated in the occurrence of idiosyncratic adverse drug reactions. The present work aimed question as whether inflammation is a determinant factor hepatic lesions induced by chlorpromazine (CPZ) using human HepaRG cell line. An state was 24-hour exposure proinflammatory cytokines interleukin-6 (IL-6) and IL-1<i>β</i>; then cells were simultaneously treated with CPZ and/or cytokine for 24 hours or daily 5 days. inflammatory response assessed induction...
The penicillinase-resistant antibiotics (PRAs), especially the highly prescribed flucloxacillin, caused frequent liver injury via mechanisms that remain largely non-elucidated. We first showed independently of cytotoxicity, could exhibit cholestatic effects in human hepatocytes absence an immune reaction, were typified by dilatation bile canaliculi associated with impairment Rho-kinase signaling pathway and reduced acid efflux. Then, we analyzed sequential molecular events involved...
The plant homeodomain zinc-finger protein, PHF6, is a transcriptional regulator, and PHF6 germline mutations cause the X-linked intellectual disability (XLID) Börjeson-Forssman-Lehmann syndrome (BFLS). mechanisms by which regulates transcription how its BFLS remain poorly characterized. Here, we show genome-wide binding of in developing cortex vicinity genes involved central nervous system development neurogenesis. Characterization mice harbouring patient reveals an increase embryonic neural...
Drug-induced intrahepatic cholestasis is characterized by cellular accumulation of bile acids (BAs), whose mechanisms remain poorly understood. The present study aimed to analyze early and progressive alterations BA profiles induced cyclosporine A, chlorpromazine, troglitazone, tolcapone, trovafloxacin, tacrolimus after 4-hour, 24-hour, 6-day treatments differentiated HepaRG cells. In BA-free medium, the potent cholestatic drugs troglitazone reduced endogenous synthesis 24 hours, whereas...
Several endothelin receptor antagonists (ERAs) have been developed for the treatment of pulmonary arterial hypertension (PAH). Some them related to clinical cases hepatocellular injury (sitaxentan [SIT]) and/or cholestasis (bosentan [BOS]). We aimed determine if ambrisentan (AMB) and macitentan (MAC), in addition BOS SIT, could potentially cause liver damage man by use human HepaRG cells. Our results showed that like BOS, MAC-induced cytotoxicity cholestatic disorders characterized bile...
Drug-induced cholestasis is mostly intrahepatic and characterized by alterations of bile canaliculi dynamics morphology as well accumulation acids (BAs) in hepatocytes. However, little information exists on first changes BA content profile induced cholestatic drugs human liver. In this study, we aimed to analyze the effects a large set noncholestatic presence physiological serum concentrations 60-fold higher levels 9 main BAs cellular using HepaRG were measured cell layers (cells +...
A dynamic model based on ordinary differential equations that describes uptake, basolateral and canalicular export of taurocholic acid (TCA) in human HepaRG cells is presented. The highly reproducible inter-assay experimental data were used to reliably estimate parameters. Primary hepatocytes similarly evaluated establish a mathematical model, but with notably higher differences TCA clearance bile canaliculi dynamics. By use the cell line, simultaneous associated sinusoidal efflux, was...
Abstract Previous studies have shown that gut‐derived bacterial endotoxins contribute in the progression of simple steatosis to steatohepatitis, although mechanism(s) remains inaccurate date. As hepatic stellate cells (HSC) play a pivotal role accumulation excessive extracellular matrix (ECM), leading collagen deposition, fibrosis, and perpetuation inflammatory response, an vitro model was developed investigate crosstalk between HSC hepatocytes (human hepatoma cell) pretreated with...
Abstract Glioblastoma (GB) remains one of the most treatment refractory and fatal tumour in humans. GB contains a population self-renewing stem cells, brain cells (BTSC) that are highly resistant to therapy at origin relapse. Here, we report, for first time, mubritinib potently impairs stemness growth patient-derived BTSCs harboring different oncogenic mutations. Mechanistically, by employing bioenergetic assays rescue experiments, provide compelling evidence acts on complex I electron...