Hepatocyte-Specific Deletion of HIF2α Prevents NASH-Related Liver Carcinogenesis by Decreasing Cancer Cell Proliferation.
HIF-2α
Hepatocellular Carcinoma
NAFLD
NASH
Journal
Cellular and molecular gastroenterology and hepatology
ISSN: 2352-345X
Titre abrégé: Cell Mol Gastroenterol Hepatol
Pays: United States
ID NLM: 101648302
Informations de publication
Date de publication:
2022
2022
Historique:
received:
06
05
2021
revised:
06
10
2021
accepted:
06
10
2021
pubmed:
17
10
2021
medline:
5
4
2022
entrez:
16
10
2021
Statut:
ppublish
Résumé
Hypoxia and hypoxia-inducible factors (HIFs) are involved in chronic liver disease progression. We previously showed that hepatocyte HIF-2α activation contributed significantly to nonalcoholic fatty liver disease progression in experimental animals and human patients. In this study, using an appropriate genetic murine model, we mechanistically investigated the involvement of hepatocyte HIF-2α in experimental nonalcoholic steatohepatitis (NASH)-related carcinogenesis. The role of HIF-2α was investigated by morphologic, cellular, and molecular biology approaches in the following: (1) mice carrying hepatocyte-specific deletion of HIF-2α (HIF-2α Mice carrying hepatocyte-specific deletion of HIF-2α (hHIF-2α These results indicate that the activation of HIF-2α in hepatocytes has a critical role in liver carcinogenesis during NASH progression, suggesting that HIF-2α-blocking agents may serve as novel putative therapeutic tools.
Sections du résumé
BACKGROUND & AIMS
Hypoxia and hypoxia-inducible factors (HIFs) are involved in chronic liver disease progression. We previously showed that hepatocyte HIF-2α activation contributed significantly to nonalcoholic fatty liver disease progression in experimental animals and human patients. In this study, using an appropriate genetic murine model, we mechanistically investigated the involvement of hepatocyte HIF-2α in experimental nonalcoholic steatohepatitis (NASH)-related carcinogenesis.
METHODS
The role of HIF-2α was investigated by morphologic, cellular, and molecular biology approaches in the following: (1) mice carrying hepatocyte-specific deletion of HIF-2α (HIF-2α
RESULTS
Mice carrying hepatocyte-specific deletion of HIF-2α (hHIF-2α
CONCLUSIONS
These results indicate that the activation of HIF-2α in hepatocytes has a critical role in liver carcinogenesis during NASH progression, suggesting that HIF-2α-blocking agents may serve as novel putative therapeutic tools.
Identifiants
pubmed: 34655812
pii: S2352-345X(21)00216-2
doi: 10.1016/j.jcmgh.2021.10.002
pmc: PMC8688724
pii:
doi:
Substances chimiques
Basic Helix-Loop-Helix Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
459-482Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.