Defective endoplasmic reticulum stress response via X box-binding protein 1 is a major cause of poor liver regeneration after partial hepatectomy in mice with non-alcoholic steatohepatitis.
endoplasmic reticulum stress response
hepatectomy
lipid droplets
liver regeneration
nonalcoholic steatohepatitis
Journal
Journal of hepato-biliary-pancreatic sciences
ISSN: 1868-6982
Titre abrégé: J Hepatobiliary Pancreat Sci
Pays: Japan
ID NLM: 101528587
Informations de publication
Date de publication:
Dec 2022
Dec 2022
Historique:
revised:
18
01
2022
received:
27
08
2021
accepted:
23
01
2022
pubmed:
25
3
2022
medline:
24
12
2022
entrez:
24
3
2022
Statut:
ppublish
Résumé
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Poor regeneration after hepatectomy in NAFLD is well recognized, but the mechanism is unclear. Endoplasmic reticulum (ER) stress plays an important role in the development of NAFLD. Here, we show that an impaired ER stress response contributes to poor liver regeneration in partially hepatectomized mice. Non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH) was induced in mice using our patented feed and 70% partial hepatectomy (PH) was performed. Mice were sacrificed 0, 4, 8, 24, or 48 hours, or 7 days after PH, and liver regeneration and the mRNA expression of ER stress markers were assessed. Non-alcoholic fatty liver disease activity score was calculated as 4-6 points for NAFL and 7 points for NASH. NASH was characterized by inflammation and high ER stress marker expression before PH. After PH, NASH mice showed poorer liver regeneration than controls. High expression of proinflammatory cytokine genes was present in NASH mice 4 hours after PH. Xbp1-s mRNA expression was high in control and NAFL mice after PH, but no higher in NASH mice. Dysfunction of the ER stress response might be a cause of poor liver regeneration in NASH.
Sections du résumé
BACKGROUND
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Poor regeneration after hepatectomy in NAFLD is well recognized, but the mechanism is unclear. Endoplasmic reticulum (ER) stress plays an important role in the development of NAFLD. Here, we show that an impaired ER stress response contributes to poor liver regeneration in partially hepatectomized mice.
METHODS
METHODS
Non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH) was induced in mice using our patented feed and 70% partial hepatectomy (PH) was performed. Mice were sacrificed 0, 4, 8, 24, or 48 hours, or 7 days after PH, and liver regeneration and the mRNA expression of ER stress markers were assessed.
RESULTS
RESULTS
Non-alcoholic fatty liver disease activity score was calculated as 4-6 points for NAFL and 7 points for NASH. NASH was characterized by inflammation and high ER stress marker expression before PH. After PH, NASH mice showed poorer liver regeneration than controls. High expression of proinflammatory cytokine genes was present in NASH mice 4 hours after PH. Xbp1-s mRNA expression was high in control and NAFL mice after PH, but no higher in NASH mice.
CONCLUSIONS
CONCLUSIONS
Dysfunction of the ER stress response might be a cause of poor liver regeneration in NASH.
Substances chimiques
RNA, Messenger
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1241-1252Subventions
Organisme : Tokushima University Graduate School of Biomedical Sciences
Informations de copyright
© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.
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