Faeces‐derived extracellular vesicles participate in the onset of barrier dysfunction leading to liver diseases - LS2N - équipe COMBI ( Combinatoire et Bio-informatique ) Accéder directement au contenu
Article Dans Une Revue Journal of Extracellular Vesicles Année : 2023

Faeces‐derived extracellular vesicles participate in the onset of barrier dysfunction leading to liver diseases

Résumé

The role of extracellular vesicles (EVs) from faeces (fEVs) and small circulating EVs (cEVs) in liver diseases such as non-alcoholic fatty diseases (NAFLD) and nonalcoholic steatohepatitis (NASH) has not been demonstrated. fEVs and cEVs of healthy donors, NAFLD and NASH patients were isolated and characterized. The effects of EVs were evaluated in intestinal, endothelial, Kupffer and stellate cells. Nonmuscular myosin light chain kinase (nmMLCK) deficient mice were used in vivo. Bacterial origins of fEVs were analysed by 16s rDNA gene sequencing. fEVs and small cEVs were composed of prokaryotic and eukaryotic origins. Only NASH-fEVs exerted deleterious effects. NASH-fEVs increased intestinal permeability and reduced expression of tight junction proteins that were prevented by nmMLCK inhibition, increased endothelial cell permeability and inflammatory cytokines and chemokines requiring TLR4/lipopolysaccharide pathway. NASH-fEVs and NASH-cEVs activated profibrotic and proinflammatory proteins of hepatic stellate cells. Treatment with NASH-fEVs evoked an increase in intestinal permeability in wild type but not in nmMLCK deficient mice. Bacterial origins of fEVs were different between NAFLD and NASH patients and 16 amplicon sequence variants were differentially abundant. We demonstrate that fEVs actively participate in barrier dysfunctions leading to liver injuries underscoring the role of nmMLCK and lipopolysaccharide carried by fEVs.
Fichier principal
Vignette du fichier
Fizanne JEV 2023.pdf (3.04 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-04118139 , version 1 (06-06-2023)

Identifiants

Citer

Lionel Fizanne, Alexandre Villard, Nadia Benabbou, Sylvain Recoquillon, Raffaella Soleti, et al.. Faeces‐derived extracellular vesicles participate in the onset of barrier dysfunction leading to liver diseases. Journal of Extracellular Vesicles, 2023, 12 (2), pp.12303. ⟨10.1002/jev2.12303⟩. ⟨hal-04118139⟩
107 Consultations
47 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More