Magnesium accumulation upon cyclin M4 silencing activates microsomal triglyceride transfer protein improving NASH.

Animals Biological Transport / drug effects Carrier Proteins / metabolism Cation Transport Proteins / metabolism Cells, Cultured Disease Models, Animal Drug Discovery Endoplasmic Reticulum Stress / drug effects Gene Expression Regulation Hepatocytes / metabolism Humans Magnesium / blood Mice Non-alcoholic Fatty Liver Disease / metabolism
CNNM4 Cyclin M4 Endoplasmic reticulum stress MTP Magnesium Microsomal triglyceride transfer protein NASH Non-alcoholic steatohepatitis Therapy siRNA

Journal

Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886

Informations de publication

Date de publication:
07 2021
Historique:
received: 20 04 2020
revised: 18 01 2021
accepted: 19 01 2021
pubmed: 12 2 2021
medline: 5 2 2022
entrez: 11 2 2021
Statut: ppublish

Résumé

Perturbations of intracellular magnesium (Mg Serum Mg Patients with NASH showed hepatic CNNM4 overexpression and dysregulated Mg CNNM4 is overexpressed in patients with NASH and is responsible for dysregulated Mg Cyclin M4 (CNNM4) is overexpressed in non-alcoholic steatohepatitis (NASH) and promotes the export of magnesium from the liver. The liver-specific silencing of Cnnm4 ameliorates NASH by reducing endoplasmic reticulum stress and promoting the activity of microsomal triglyceride transfer protein.

Sections du résumé

BACKGROUND & AIMS
Perturbations of intracellular magnesium (Mg
METHODS
Serum Mg
RESULTS
Patients with NASH showed hepatic CNNM4 overexpression and dysregulated Mg
CONCLUSIONS
CNNM4 is overexpressed in patients with NASH and is responsible for dysregulated Mg
LAY SUMMARY
Cyclin M4 (CNNM4) is overexpressed in non-alcoholic steatohepatitis (NASH) and promotes the export of magnesium from the liver. The liver-specific silencing of Cnnm4 ameliorates NASH by reducing endoplasmic reticulum stress and promoting the activity of microsomal triglyceride transfer protein.

Identifiants

DOI: 10.1016/j.jhep.2021.01.043 PMID: 33571553 PMC: PMC8217299
pubmed: 33571553
pii: S0168-8278(21)00094-5
doi: 10.1016/j.jhep.2021.01.043
pmc: PMC8217299
mid: NIHMS1694309
pii:
doi:

Substances chimiques

CNNM4 protein, human 0
Carrier Proteins 0
Cation Transport Proteins 0
Cnnm4 protein, mouse 0
microsomal triglyceride transfer protein 0
Magnesium I38ZP9992A

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

34-45

Subventions

Organisme : NCI NIH HHS
ID : R01 CA217817
Pays : United States

Informations de copyright

Copyright © 2021 European Association for the Study of the Liver. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of interest The authors declare no conflicts of interest related to this submitted work. Please refer to the accompanying ICMJE disclosure forms for further details.

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Auteurs

Jorge Simón (J)

Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160, Bizkaia, Spain.

Naroa Goikoetxea-Usandizaga (N)

Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain.

Marina Serrano-Maciá (M)

Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain.

David Fernández-Ramos (D)

Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160, Bizkaia, Spain; Precision Medicine and Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain.

Diego Sáenz de Urturi (D)

Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.

Jessica J Gruskos (JJ)

Department of Chemistry, New York University, New York, NY, USA.

Pablo Fernández-Tussy (P)

Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain.

Sofía Lachiondo-Ortega (S)

Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain.

Irene González-Recio (I)

Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain.

Rubén Rodríguez-Agudo (R)

Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain.

Virginia Gutiérrez-de-Juan (V)

Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain.

Begoña Rodríguez-Iruretagoyena (B)

Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain.

Marta Varela-Rey (M)

Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160, Bizkaia, Spain.

Paula Gimenez-Mascarell (P)

Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain.

María Mercado-Gomez (M)

Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain.

Beatriz Gómez-Santos (B)

Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.

Carmen Fernandez-Rodriguez (C)

Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain.

Fernando Lopitz-Otsoa (F)

Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain; Precision Medicine and Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain.

Maider Bizkarguenaga (M)

Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain; Precision Medicine and Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain.

Sibylle Dames (S)

Silence Therapeutics GmbH, Berlin, Germany.

Ute Schaeper (U)

Silence Therapeutics GmbH, Berlin, Germany.

Franz Martin (F)

Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad Pablo de Olavide, Universidad de Sevilla, Consejo Superior de Investigaciones Científicas (CSIC), Seville, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain.

Guadalupe Sabio (G)

Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.

Paula Iruzubieta (P)

Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, Santander, Spain; Clinical and Translational Digestive Research Group, Instituto de Investigación Sanitaria Valdecilla (IDIVAL), Santander, Spain.

Javier Crespo (J)

Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, Santander, Spain; Clinical and Translational Digestive Research Group, Instituto de Investigación Sanitaria Valdecilla (IDIVAL), Santander, Spain.

Patricia Aspichueta (P)

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160, Bizkaia, Spain; Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain; Biocruces Health Research Institute, Barakaldo, Bizkaia, Spain.

Kevan H-Y Chu (KH)

Department of Chemistry, New York University, New York, NY, USA.

Daniela Buccella (D)

Department of Chemistry, New York University, New York, NY, USA.

César Martín (C)

Instituto Biofisika (UPV/EHU, CSIC) and Departamento de Bioquímica, Universidad del País Vasco, Bilbao, Spain.

Teresa Cardoso Delgado (TC)

Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain.

Luis Alfonso Martínez-Cruz (LA)

Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain.

María Luz Martínez-Chantar (ML)

Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160, Bizkaia, Spain. Electronic address: mlmartinez@cicbiogune.es.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Magnesium accumulation upon cyclin M4...
questionsmedicales.fr › Métabolisme › Transport biologique › Magnesium accumulation upon cyclin M4...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de transport › Magnesium accumulation upon cyclin M4...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Pompes ioniques › Transporteurs de cations › Magnesium accumulation upon cyclin M4...
questionsmedicales.fr › Cellules › Cellules cultivées › Magnesium accumulation upon cyclin M4...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Magnesium accumulation upon cyclin M4...
questionsmedicales.fr › Techniques d'investigation › Développement de médicament › Découverte de médicament › Magnesium accumulation upon cyclin M4...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Stress du réticulum endoplasmique › Magnesium accumulation upon cyclin M4...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Magnesium accumulation upon cyclin M4...
questionsmedicales.fr › Cellules › Cellules épithéliales › Hépatocytes › Magnesium accumulation upon cyclin M4...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Magnesium accumulation upon cyclin M4...
questionsmedicales.fr › Produits chimiques inorganiques › Métaux › Métaux légers › Magnésium › Magnesium accumulation upon cyclin M4...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Magnesium accumulation upon cyclin M4...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Stéatose hépatique › Stéatose hépatique non alcoolique › Magnesium accumulation upon cyclin M4...