Title :

Liver microRNA-21 is overexpressed in non-alcoholic steatohepatitis and contributes to the disease in experimental models by inhibiting PPARα expression

Author(s) :

Loyer, Xavier [Auteur]
Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)]
Paradis, Valérie [Auteur]
Centre de recherche biomédicale Bichat-Beaujon [CRB3]
Hôpital Beaujon [AP-HP]
Hénique, Carole [Auteur]
Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)]
Vion, Anne-Clémence [Auteur]
Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)]
Colnot, Nathalie [Auteur]
Hôpital Beaujon [AP-HP]
Guerin, Coralie [Auteur]
Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)]
Devue, Cécile [Auteur]
Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)]
On, Sissi [Auteur]
Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)]
Scetbun, Jérémy [Auteur]
Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)]
Romain, Mélissa [Auteur]
Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)]
Paul, Jean-Louis [Auteur]
Hôpital Européen Georges Pompidou [APHP] [HEGP]
Rothenberg, Marc [Auteur]
University of Cincinnati College of Medicine
Marcellin, Patrick [Auteur]
Hôpital Beaujon [AP-HP]
Centre de recherche biomédicale Bichat-Beaujon [CRB3]
Durand, François [Auteur]
Hôpital Beaujon [AP-HP]
Centre de recherche biomédicale Bichat-Beaujon [CRB3]
Bedossa, Pierre [Auteur]
Centre de recherche biomédicale Bichat-Beaujon [CRB3]
Hôpital Beaujon [AP-HP]
Prip-Buus, Carina [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Baugé, Eric [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires [RNMCD - U1011]
Staels, Bart [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires [RNMCD - U1011]
Boulanger, Chantal [Auteur]
Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)]
Tedgui, Alain [Auteur]
Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)]
Rautou, Pierre-Emmanuel [Auteur]
Hôpital Beaujon [AP-HP]
Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)]

Journal title :

Gut

Pages :

1882-1894

Publisher :

BMJ Publishing Group

Publication date :

2016-10-07

ISSN :

0017-5749

English keyword(s) :

FATTY LIVER
INFLAMMATION
NONALCOHOLIC STEATOHEPATITIS

HAL domain(s) :

Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Hépatologie et Gastroentérologie

English abstract : [en]

Objective: Previous studies suggested that microRNA-21 may be upregulated in the liver in non-alcoholic steatohepatitis (NASH), but its role in the development of this disease remains unknown. This study aimed to determine ...
Show more >Objective: Previous studies suggested that microRNA-21 may be upregulated in the liver in non-alcoholic steatohepatitis (NASH), but its role in the development of this disease remains unknown. This study aimed to determine the role of microRNA-21 in NASH.Design: We inhibited or suppressed microRNA-21 in different mouse models of NASH: (a) low-density lipoprotein receptor-deficient (Ldlr-/-) mice fed a high-fat diet and treated with antagomir-21 or antagomir control; (b) microRNA-21-deficient and wild-type mice fed a methionine-choline-deficient (MCD) diet; (c) peroxisome proliferation-activator receptor α (PPARα)-deficient mice fed an MCD diet and treated with antagomir-21 or antagomir control. We assessed features of NASH and determined liver microRNA-21 levels and cell localisation. MicroRNA-21 levels were also quantified in the liver of patients with NASH, bland steatosis or normal liver and localisation was determined.Results: Inhibiting or suppressing liver microRNA-21 expression reduced liver cell injury, inflammation and fibrogenesis without affecting liver lipid accumulation in Ldlr-/- fed a high-fat diet and in wild-type mice fed an MCD diet. Liver microRNA-21 was overexpressed, primarily in biliary and inflammatory cells, in mouse models as well as in patients with NASH, but not in patients with bland steatosis. PPARα, a known microRNA-21 target, implicated in NASH, was decreased in the liver of mice with NASH and restored following microRNA-21 inhibition or suppression. The effect of antagomir-21 was lost in PPARα-deficient mice.Conclusions: MicroRNA-21 inhibition or suppression decreases liver injury, inflammation and fibrosis, by restoring PPARα expression. Antagomir-21 might be a future therapeutic strategy for NASH.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (EGID) - U1011

Source :

Harvested from HAL