Rapid recapitulation of non-alcoholic steatohepatitis upon loss of HCF-1 function in mice.

Détails

Ressource 1Télécharger: e00405-18.full.pdf (10219.06 [Ko])
Etat: Serval
Version: Final published version
ID Serval
serval:BIB_212558107C3D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Rapid recapitulation of non-alcoholic steatohepatitis upon loss of HCF-1 function in mice.
Périodique
Molecular and Cellular Biology
Auteur(s)
Minocha S., Villeneuve D., Praz V., Moret C., Lopes M., Pinatel D., Rib L., Guex N., Herr W.
ISSN
1098-5549 (Electronic)
ISSN-L
0270-7306
Statut éditorial
Publié
Date de publication
2018
Peer-reviewed
Oui
Volume
39
Numéro
5
Pages
UNSP e00405
Langue
anglais
Résumé
Host-cell factor 1 (HCF-1), encoded by the ubiquitously expressed X-linked gene Hcfc1, is an epigenetic co-regulator important for mouse development and cell proliferation, including during liver regeneration. We used a hepatocyte-specific inducible Hcfc1 knock-out allele (called Hcfc1 <sup>hepKO</sup> ), to induce HCF-1 loss in hepatocytes of hemizygous Hcfc1 <sup>hepKO/Y</sup> males by four days. In heterozygous Hcfc1 <sup>hepKO/+</sup> females, owing to random X-chromosome inactivation, upon Hcfc1 <sup>hepKO</sup> allele induction, a 50/50 mix of HCF-1 positive and negative hepatocyte clusters is engineered. The livers with Hcfc1 <sup>hepKO/Y</sup> hepatocytes displayed a 21-24-day terminal non-alcoholic fatty liver (NAFL) followed by non-alcoholic steatohepatitis (NASH) disease progression typical of severe NAFL disease (NAFLD). In contrast, in livers with heterozygous Hcfc1 <sup>hepKO/+</sup> hepatocytes, HCF-1-positive hepatocytes replaced HCF-1-negative hepatocytes and revealed only mild-NAFL development. Loss of HCF-1 led to loss of PGC1α protein, probably owing to its destabilization, and deregulation of gene expression particularly of genes involved in mitochondrial structure and function, likely explaining the severe Hcfc1 <sup>hepKO/Y</sup> liver pathology. Thus, HCF-1 is essential for hepatocyte function, likely playing both transcriptional and non-transcriptional roles. These genetically-engineered loss-of-HCF-1 mice can be used to study NASH as well as NAFLD resolution.
Mots-clé
HCF-1, Hcfc1, NAFLD, NASH, PGC1alpha, chromatin, gene expression, steatosis
Pubmed
Web of science
Open Access
Oui
Création de la notice
14/01/2019 18:45
Dernière modification de la notice
08/05/2019 15:38
Données d'usage