RT Journal Article
T1 Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury
A1 Lamas Paz, Arantza
A1 Morán, Laura
A1 Salinas Rodríguez, Beatriz
A1 López Alcántara, Nuria
A1 Asensio, Iris
A1 Fengjie, Hao
A1 Kang, Zheng
A1 Martín Adrados, Beatriz
A1 Moreno Gutiérrez, Laura
A1 Cogolludo Torralba, Ángel Luis
A1 Gómez Del Moral Martín-Consuegra, Manuel María
A1 Martínez Naves, Eduardo
A1 Vaquero Martín, Francisco Javier
A1 Bañares Cañizares, Rafael
A1 Nevzorova, Yulia
A1 Cubero Palero, Francisco Javier
AB 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
PB Frontiers Media
SN 1663-9812
YR 2020
FD 2020-12-21
LK https://hdl.handle.net/20.500.14352/92415
UL https://hdl.handle.net/20.500.14352/92415
LA eng
NO 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, Cubero FJ. Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury. Front Pharmacol. 2020 Dec 21;11:603771. doi: 10.3389/fphar.2020.603771
NO Ministerio de Economía, Comercio y Empresa
NO Universidad Complutense de Madrid
NO German Research Foundation
DS Docta Complutense
RD 21 ago 2024