Titre :

Mitochondrial antiviral signaling protein enhances MASLD progression via the ERK/TNFα/NFκβ pathway.

Auteur(s) :

Nóvoa, Eva [Auteur]
Da Silva Lima, Natalia [Auteur]
Gonzalez-Rellan, Maria J. [Auteur]
Chantada-Vazquez, Maria D. P. [Auteur]
Verheij, Joanne [Auteur]
Rodriguez, Amaia [Auteur]
Esquinas-Roman, Eva M. [Auteur]
Fondevila, Marcos F. [Auteur]
Koning, Mirja [Auteur]
Fernandez, Uxia [Auteur]
Cabaleiro, Alba [Auteur]
Parracho, Tamara [Auteur]
Iglesias-Moure, Jose [Auteur]
Seoane, Samuel [Auteur]
Porteiro, Begona [Auteur]
Escudero, Adriana [Auteur]
Senra, Ana [Auteur]
Perez-Fernandez, Roman [Auteur]
López, Miguel [Auteur]
Fidalgo, Miguel [Auteur]
Guallar, Diana [Auteur]
Martinez-Chantar, Maria L. [Auteur]
Dieguez, Carlos [Auteur]
Varela-Rey, Marta [Auteur]
Prevot, Vincent [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Schwaninger, Markus [Auteur]
Meijnikman, Abraham [Auteur]
Bravo, Susana B. [Auteur]
Frühbeck, Gema [Auteur]
Nogueiras, Ruben [Auteur]

Titre de la revue :

Hepatology (Baltimore, Md.)

Nom court de la revue :

Hepatology

Date de publication :

2024-07-28

ISSN :

1527-3350

Mot(s)-clé(s) en anglais :

MAVS
MASLD
NF kappa beta
TNF
hepatocytes

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Background and Aims: Mitochondrial antiviral signaling protein (MAVS) is a critical regulator that activates the host’s innate immunity against RNA viruses, and its signaling pathway has been linked to the secretion of ...
Lire la suite >Background and Aims: Mitochondrial antiviral signaling protein (MAVS) is a critical regulator that activates the host’s innate immunity against RNA viruses, and its signaling pathway has been linked to the secretion of proinflammatory cytokines. However, the actions of MAVS on inflammatory pathways during the development of metabolic dysfunction–associated steatotic liver disease (MASLD) have been little studied. Approach and Results: Liver proteomic analysis of mice with genetically manipulated hepatic p63, a transcription factor that induces liver steatosis, revealed MAVS as a target downstream of p63. MAVS was thus further evaluated in liver samples from patients and in animal models with MASLD. Genetic inhibition of MAVS was performed in hepatocyte cell lines, primary hepatocytes, spheroids, and mice. MAVS expression is induced in the liver of both animal models and people with MASLD as compared with those without liver disease. Using genetic knockdown of MAVS in adult mice ameliorates diet-induced MASLD. In vitro, silencing MAVS blunts oleic and palmitic acid–induced lipid content, while its overexpression increases the lipid load in hepatocytes. Inhibiting hepatic MAVS reduces circulating levels of the proinflammatory cytokine TNFα and the hepatic expression of both TNFα and NFκβ. Moreover, the inhibition of ERK abolished the activation of TNFα induced by MAVS. The posttranslational modification O-GlcNAcylation of MAVS is required to activate inflammation and to promote the high lipid content in hepatocytes. Conclusions: MAVS is involved in the development of steatosis, and its inhibition in previously damaged hepatocytes can ameliorate MASLD.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Date de dépôt :

2024-06-24T21:04:33Z
2025-01-09T12:48:10Z