A5030185746- Neonatal Health and Biochemistry
- Biomedical Research and Pathophysiology
- Amino Acid Enzymes and Metabolism
- Extracellular vesicles in disease
- Erythrocyte Function and Pathophysiology
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Virus-based gene therapy research
- Nanoplatforms for cancer theranostics
- MicroRNA in disease regulation
- RNA Interference and Gene Delivery
- Pulmonary Hypertension Research and Treatments
- Viral Infections and Immunology Research
- Viral Infectious Diseases and Gene Expression in Insects
- Cardiac Valve Diseases and Treatments
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Cell Adhesion Molecules Research
- Angiogenesis and VEGF in Cancer
- Neonatal Respiratory Health Research
- Zebrafish Biomedical Research Applications
- Complement system in diseases
- Histone Deacetylase Inhibitors Research
- Nitric Oxide and Endothelin Effects
- Eicosanoids and Hypertension Pharmacology
- Reproductive System and Pregnancy
Université Paris Cité
2009-2023
Inserm
2013-2023
Institut Curie
2020-2022
Université Paris Sciences et Lettres
2020-2022
Centre National de la Recherche Scientifique
2022
Hôpital Européen
2020
European Genomic Institute for Diabetes
2020
European Investment Bank
2020
Immunité et Cancer
2020
Assistance Publique – Hôpitaux de Paris
2020
Abstract Despite their roles in intercellular communications, the different populations of extracellular vesicles (EVs) and secretion mechanisms are not fully characterized: how to what extent EVs form as intraluminal endocytic compartments (exosomes), or at plasma membrane (PM) (ectosomes) remains unclear. Here we follow intracellular trafficking EV markers CD9 CD63 from endoplasmic reticulum residency compartment, respectively PM late endosomes. We observe transient co-localization both...
Significance Our work uncovers mechanisms by which tumor cells impact tumor-associated macrophages in human triple-negative breast cancer. Via extracellular vesicles (EVs), these tumors promote with proinflammatory features, correlated better clinical outcome. results suggest exploration of EVs as tools, alone, or combination other therapies, to a favorable environment for the generation anti-tumor immune responses.
Abstract The endolysosomal system sustains the reabsorptive activity of specialized epithelial cells. Lysosomal storage diseases such as nephropathic cystinosis cause a major dysfunction cells lining kidney tubule, resulting in massive losses vital solutes urine. mechanisms linking lysosomal defects and remain unknown, preventing development disease-modifying therapies. Here we demonstrate, by combining genetic pharmacologic approaches, that results defective autophagy-mediated clearance...
Abstract SARS‐CoV‐2 entry is mediated by binding of the spike protein (S) to surface receptor ACE2 and subsequent priming host TMPRSS2 allowing membrane fusion. Here, we produced extracellular vesicles (EVs) exposing demonstrate that ACE2‐EVs are efficient decoys for S protein‐containing lentivirus. Reduction infectivity positively correlates with level ACE2, much more than soluble further enhanced inclusion TMPRSS2.
Background. Cystinosis is caused by mutations in CTNS that encodes cystinosin, the lysosomal cystine transporter. The most severe and frequent form characterized a proximal tubulopathy appears around 6 to 12 months of age. In absence treatment, end-stage renal disease reached 10 years. Ctns−/− mice mixed 129Sv × C57BL/6 genetic background show elevated levels; however, or not observed.
Cystinosis is a rare autosomal recessive storage disorder characterized by defective lysosomal efflux of cystine due to mutations in the CTNS gene encoding transporter, cystinosin. Lysosomal accumulation leads crystal formation and functional impairment multiple organs. Moreover, cystinosis most common inherited cause renal Fanconi syndrome children. Oral cysteamine therapy delays disease progression reducing intracellular levels. However, because does not correct all complications...
Nephropathic cystinosis, a lysosomal storage disease caused by mutations in the CTNS gene encoding cystine transporter cystinosin, is characterized generalized proximal tubule (PT) dysfunction that progresses, if untreated, to end-stage renal disease. The pathogenesis of defective PT cellular transport nephropathic cystinosis remains unclear. We recently generated line C57BL/6 Ctns mice and analyzed endocytic uptake, lysosome function, dedifferentiation proliferation markers using primary...
Cystinosis, a main cause of Fanconi syndrome, is reproduced in congenic C57BL/6 cystinosin knockout (KO) mice. To identify the sequence pathogenic and adaptation mechanisms nephropathic cystinosis, we defined onset syndrome KO mice between 3 6 months age analyzed correlation with structural functional changes proximal tubular cells (PTCs), focus on endocytosis ultrafiltrated disulfide-rich proteins as key source cystine. Despite considerable variation at same age, typical event sequences...
Cells release diverse types of extracellular vesicles (EVs), which transfer complex signals to surrounding cells. Specific markers distinguish different EVs (e.g. exosomes, ectosomes, enveloped viruses like HIV) are still lacking. We have developed a proteomic profiling approach for characterizing EV subtype composition and applied it human Jurkat T generated an interactive database define groups proteins with similar profiles, suggesting in EVs. Biochemical validation confirmed the presence...
Background —Intimal hyperplasia after stent implantation is the main cause of in-stent restenosis. Activated monocytes play a key role in intimal growth. The anti-inflammatory cytokine interleukin-10 (IL-10) potent monocyte deactivator, endogenously produced atherosclerotic plaque. We tested hypothesis that exogenous IL-10 may limit postangioplasty balloon angioplasty or stenting. Methods and Results —Hypercholesterolemic rabbits were treated with recombinant human (rhuIL-10) for 3 days 28...
Cystinosis is an inherited disorder resulting from a mutation in the CTNS gene, causing progressive proximal tubular cell flattening, so-called swan-neck lesion (SNL), and eventual renal failure. To determine role of oxidative stress cystinosis, histologic sections kidneys C57BL/6 Ctns −/− wild-type mice were examined by immunohistochemistry morphometry 1 wk to 20 mo age. Additional treated 6 with vehicle or mitoquinone (MitoQ), antioxidant targeted mitochondria. The leading edge SNL lost...
Abstract Thyroid hormones are released from thyroglobulin (Tg) in lysosomes, which impaired infantile/nephropathic cystinosis. Cystinosis is a lysosomal cystine storage disease due to defective exporter, cystinosin. Cystinotic children develop subclinical and then overt hypothyroidism. Why hypothyroidism the most frequent earliest endocrine complication of cystinosis unknown. We here defined early alterations Ctns−/− mice thyroid identified subcellular molecular mechanisms. At 9 months, T4...
The study's aim was to analyze the capacity of human valve interstitial cells (VICs) participate in aortic angiogenesis. Approach and Results: VICs were isolated from valves obtained after surgery for calcific disease normal unsuitable grafting (control VICs). We examined VIC vitro vivo potential differentiate endothelial perivascular lineages. paracrine effect also on colony-forming cells. A pathological (VIC
Eukaryotic cells, including cancer secrete highly heterogeneous populations of extracellular vesicles (EVs). EVs could have different subcellular origin, composition and functional properties, but tools to distinguish between EV subtypes are scarce. Here, we tagged CD63- or CD9-positive secreted by triple negative breast cells with Nanoluciferase enzyme, set-up a miniaturized method quantify secretion these two directly in the supernatant cells. We performed cell-based high-content screening...
Summary: Nebivolol is a highly selective β1-adrenoreceptor-blocking agent with peculiar pharmacodynamic profile. It has peripheral acute vasodilating properties that are mediated by modulation of the endogenous production nitric oxide. In this study we analyzed different signaling pathways implicated in response human umbilical vein endothelial cells to nebivolol. Its effect on transduction was determined assaying phospholipase C and A2 activities cyclic adenosine monophosphate (AMP)...
Efficient and homogeneous gene transfer to cardiac myocytes is a major target in myocardial therapy. The aim of this study was determine the conditions permitting efficient, homogeneous, adenovirus-mediated myocytes, with view application during coronary artery catheterization. Gene adult rat ventricular conducted using type 5 adenoviruses carrying lacZ reporter gene. Adenovirus delivery via arteries performed on isolated perfused hearts, efficiency analyzed whole ventricles, freshly...
Cystinosis is a rare autosomal recessive lysosomal storage disorder characterized by intralysosomal accumulation of cystine. The causative gene for cystinosis CTNS, which encodes the protein cystinosin, proton-driven cystine transporter. Over 100 mutations have been reported, leading to varying disease severity, often in correlation with residual cystinosin activity as transporter and maintenance its protein-protein interactions. In this study, we focus on ΔITILELP mutation, only mutation...
Significance Statement Nephropathic cystinosis is the result of deletion or inactivating mutations gene encoding lysosomal cystine transporter cystinosin, but extent to which disease progression depends on accumulation transport-independent effects cystinosin unknown. Cysteamine, current treatment prevent accumulation, delays renal failure does not correct Fanconi syndrome nor it provide a cure. The authors demonstrate that suppression endocytosis in kidney proximal tubular cells...