Production of Elastin-Derived Peptides Contributes to the Development of Nonalcoholic Steatohepatitis
| Autor: | Jean-Louis Guéant, V. Durlach, Pascal Maurice, Béatrice Romier, Laurent Duca, Roselyne Garnotel, Jean-Pierre Bronowicki, Alexandre Guillot, Eric Bertin, Sébastien Blaise, Andrea Heinz, Laurent Martiny, Jessica Jonquet, Hervé Sartelet, Christian E.H. Schmelzer, Johanne Amoyel, Laurent Debelle, Corinne Ivaldi, Jean Marc Alberto, Thinhinane Hocine, Amar Bennasroune |
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| Přispěvatelé: | Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Universitaire de Reims (CHU Reims), Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Joliot Curie, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Martin-Luther-University Halle-Wittenberg, Fraunhofer Institute for Microstructure of Materials and Systems IMWS, SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Publica |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Endocrinology Diabetes and Metabolism [SDV]Life Sciences [q-bio] [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] Body Mass Index Cohort Studies Liver disease Non-alcoholic Fatty Liver Disease Fibrosis Nonalcoholic fatty liver disease [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] Cells Cultured ComputingMilieux_MISCELLANEOUS education.field_of_study biology Extracellular Matrix Obesity Morbid 3. Good health [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biophysics Liver Lipogenesis Disease Progression Female medicine.symptom [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing Signal Transduction medicine.medical_specialty [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph] Population Receptors Cell Surface Inflammation [SDV.CAN]Life Sciences [q-bio]/Cancer Diet High-Fat Proof of Concept Study 03 medical and health sciences Insulin resistance Internal medicine Internal Medicine medicine Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology education business.industry medicine.disease Mice Mutant Strains Peptide Fragments Elastin Mice Inbred C57BL 030104 developmental biology Endocrinology Diabetes Mellitus Type 2 Gene Expression Regulation biology.protein [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic business Biomarkers |
| Zdroj: | Diabetes Diabetes, American Diabetes Association, 2018, 67 (8), pp.1604-1615. ⟨10.2337/db17-0490⟩ Diabetes, American Diabetes Association, 2018, ⟨10.2337/db17-0490⟩ Diabetes, American Diabetes Association, 2018, 67 (8), pp.1604-1615 |
| ISSN: | 0012-1797 |
| DOI: | 10.2337/db17-0490⟩ |
| Popis: | Affecting more than 30% of the Western population, nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and can lead to multiple complications, including nonalcoholic steatohepatitis (NASH), cancer, hypertension, and atherosclerosis. Insulin resistance and obesity are described as potential causes of NAFLD. However, we surmised that factors such as extracellular matrix remodeling of large blood vessels, skin, or lungs may also participate in the progression of liver diseases. We studied the effects of elastin-derived peptides (EDPs), biomarkers of aging, on NAFLD progression. We evaluated the consequences of EDP accumulation in mice and of elastin receptor complex (ERC) activation on lipid storage in hepatocytes, inflammation, and fibrosis development. The accumulation of EDPs induces hepatic lipogenesis (i.e., SREBP1c and ACC), inflammation (i.e., Kupffer cells, IL-1β, and TGF-β), and fibrosis (collagen and elastin expression). These effects are induced by inhibition of the LKB1-AMPK pathway by ERC activation. In addition, pharmacological inhibitors of EDPs demonstrate that this EDP-driven lipogenesis and fibrosis relies on engagement of the ERC. Our data reveal a major role of EDPs in the development of NASH, and they provide new clues for understanding the relationship between NAFLD and vascular aging. |
| Databáze: | OpenAIRE |
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