Cargando…

Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Lamas-Paz, Arantza, Morán, Laura, Peng, Jin, Salinas, Beatriz, López-Alcántara, Nuria, Sydor, Svenja, Vilchez-Vargas, Ramiro, Asensio, Iris, Hao, Fengjie, Zheng, Kang, Martín-Adrados, Beatriz, Moreno, Laura, Cogolludo, Angel, Gómez del Moral, Manuel, Bechmann, Lars, Martínez-Naves, Eduardo, Vaquero, Javier, Bañares, Rafael, Nevzorova, Yulia A., Cubero, Francisco Javier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779758/
https://www.ncbi.nlm.nih.gov/pubmed/33408632
http://dx.doi.org/10.3389/fphar.2020.603771
_version_ 1783631391539331072
author Lamas-Paz, Arantza
Morán, Laura
Peng, Jin
Salinas, Beatriz
López-Alcántara, Nuria
Sydor, Svenja
Vilchez-Vargas, Ramiro
Asensio, Iris
Hao, Fengjie
Zheng, Kang
Martín-Adrados, Beatriz
Moreno, Laura
Cogolludo, Angel
Gómez del Moral, Manuel
Bechmann, Lars
Martínez-Naves, Eduardo
Vaquero, Javier
Bañares, Rafael
Nevzorova, Yulia A.
Cubero, Francisco Javier
author_facet Lamas-Paz, Arantza
Morán, Laura
Peng, Jin
Salinas, Beatriz
López-Alcántara, Nuria
Sydor, Svenja
Vilchez-Vargas, Ramiro
Asensio, Iris
Hao, Fengjie
Zheng, Kang
Martín-Adrados, Beatriz
Moreno, Laura
Cogolludo, Angel
Gómez del Moral, Manuel
Bechmann, Lars
Martínez-Naves, Eduardo
Vaquero, Javier
Bañares, Rafael
Nevzorova, Yulia A.
Cubero, Francisco Javier
author_sort Lamas-Paz, Arantza
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7779758
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-77797582021-01-05 Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury Lamas-Paz, Arantza Morán, Laura Peng, Jin Salinas, Beatriz López-Alcántara, Nuria Sydor, Svenja Vilchez-Vargas, Ramiro Asensio, Iris Hao, Fengjie Zheng, Kang Martín-Adrados, Beatriz Moreno, Laura Cogolludo, Angel Gómez del Moral, Manuel Bechmann, Lars Martínez-Naves, Eduardo Vaquero, Javier Bañares, Rafael Nevzorova, Yulia A. Cubero, Francisco Javier Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2020-12-21 /pmc/articles/PMC7779758/ /pubmed/33408632 http://dx.doi.org/10.3389/fphar.2020.603771 Text en 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 http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Lamas-Paz, Arantza
Morán, Laura
Peng, Jin
Salinas, Beatriz
López-Alcántara, Nuria
Sydor, Svenja
Vilchez-Vargas, Ramiro
Asensio, Iris
Hao, Fengjie
Zheng, Kang
Martín-Adrados, Beatriz
Moreno, Laura
Cogolludo, Angel
Gómez del Moral, Manuel
Bechmann, Lars
Martínez-Naves, Eduardo
Vaquero, Javier
Bañares, Rafael
Nevzorova, Yulia A.
Cubero, Francisco Javier
Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury
title Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury
title_full Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury
title_fullStr Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury
title_full_unstemmed Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury
title_short Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury
title_sort intestinal epithelial cell-derived extracellular vesicles modulate hepatic injury via the gut-liver axis during acute alcohol injury
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779758/
https://www.ncbi.nlm.nih.gov/pubmed/33408632
http://dx.doi.org/10.3389/fphar.2020.603771
work_keys_str_mv AT lamaspazarantza intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury
AT moranlaura intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury
AT pengjin intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury
AT salinasbeatriz intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury
AT lopezalcantaranuria intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury
AT sydorsvenja intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury
AT vilchezvargasramiro intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury
AT asensioiris intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury
AT haofengjie intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury
AT zhengkang intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury
AT martinadradosbeatriz intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury
AT morenolaura intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury
AT cogolludoangel intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury
AT gomezdelmoralmanuel intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury
AT bechmannlars intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury
AT martineznaveseduardo intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury
AT vaquerojavier intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury
AT banaresrafael intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury
AT nevzorovayuliaa intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury
AT cuberofranciscojavier intestinalepithelialcellderivedextracellularvesiclesmodulatehepaticinjuryviathegutliveraxisduringacutealcoholinjury