2024-03-29T14:57:06Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/132452022-10-06T11:33:02Zcom_20.500.12105_2152com_20.500.12105_2051com_20.500.12105_2144col_20.500.12105_2153
Repisalud
author
Lamas-Paz, Arantza
author
Moran, Laura
author
Peng, Jin
author
Salinas, Beatriz
author
Lopez-Alcantara, Nuria
author
Sydor, Svenja
author
Vilchez-Vargas, Ramiro
author
Asensio, Iris
author
Hao, Fengjie
author
Zheng, Kang
author
Martin-Adrados, Beatriz
author
Moreno, Laura
author
Cogolludo, Angel
author
Gomez Del Moral, Manuel
author
Bechmann, Lars
author
Martinez-Naves, Eduardo
author
Vaquero, Javier
author
Bañares, Rafael
author
Nevzorova, Yulia A
author
Cubero, Francisco Javier
funder
Consorcio NanoLiver-CM
funder
Deutsche Forschungsgemeinschaft (Alemania)
funder
Chinese Scholarship Council
funder
Natural Science Foundation of Jiangsu Province (China)
funder
Ministerio de Asuntos Económicos y Transformación Digital (España)
2021-07-15T11:40:06Z
2021-07-15T11:40:06Z
2020-12
Front Pharmacol. 2020; 11:603771
1663-9812
http://hdl.handle.net/20.500.12105/13245
33408632
10.3389/fphar.2020.603771
Frontiers in 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.
eng
Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury.
journal article
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URL
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