1. Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury.
- Author
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Lamas-Paz A, Morán L, Peng J, Salinas B, López-Alcántara N, Sydor S, Vilchez-Vargas R, Asensio I, Hao F, Zheng K, Martín-Adrados B, Moreno L, Cogolludo A, Gómez Del Moral M, Bechmann L, Martínez-Naves E, Vaquero J, Bañares R, Nevzorova YA, and Cubero FJ
- Abstract
Binge drinking, i.e., heavy episodic drinking in a short time, has recently become an alarming societal problem with negative health impact. However, the harmful effects of acute alcohol injury in the gut-liver axis remain elusive. Hence, we focused on the physiological and pathological changes and the underlying mechanisms of experimental binge drinking in the context of the gut-liver axis. Eight-week-old mice with a C57BL/6 background received a single dose (p.o.) of ethanol (EtOH) [6 g/kg b.w.] as a preclinical model of acute alcohol injury. Controls received a single dose of PBS. Mice were sacrificed 8 h later. In parallel, HepaRGs and Caco-2 cells, human cell lines of differentiated hepatocytes and intestinal epithelial cells intestinal epithelial cells (IECs), respectively, were challenged in the presence or absence of EtOH [0-100 mM]. Extracellular vesicles (EVs) isolated by ultracentrifugation from culture media of IECs were added to hepatocyte cell cultures. Increased intestinal permeability, loss of zonula occludens-1 (ZO-1) and MUCIN-2 expression, and alterations in microbiota-increased Lactobacillus and decreased Lachnospiraceae species-were found in the large intestine of mice exposed to EtOH. Increased TUNEL-positive cells, infiltration of CD11b-positive immune cells, pro-inflammatory cytokines (e.g., tlr4 , tnf , il1β ), and markers of lipid accumulation (Oil Red O, srbep1 ) were evident in livers of mice exposed to EtOH, particularly in females. In vitro experiments indicated that EVs released by IECs in response to ethanol exerted a deleterious effect on hepatocyte viability and lipid accumulation. Overall, our data identified a novel mechanism responsible for driving hepatic injury in the gut-liver axis, opening novel avenues for therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Lamas-Paz, Morán, Peng, Salinas, López-Alcántara, Sydor, Vilchez-Vargas, Asensio, Hao, Zheng, Martín-Adrados, Moreno, Cogolludo, Gómez del Moral, Bechmann, Martínez-Naves, Vaquero, Bañares, Nevzorova and Cubero.)
- Published
- 2020
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