A novel prostaglandin I
Non-alcoholic steatohepatitis
ONO-1301
Prostacyclin
Prostaglandin E2
Prostaglandin I2
Journal
Inflammation and regeneration
ISSN: 1880-9693
Titre abrégé: Inflamm Regen
Pays: England
ID NLM: 101479577
Informations de publication
Date de publication:
01 Feb 2022
01 Feb 2022
Historique:
received:
23
08
2021
accepted:
20
12
2021
entrez:
1
2
2022
pubmed:
2
2
2022
medline:
2
2
2022
Statut:
epublish
Résumé
ONO-1301 is a novel long-lasting prostaglandin (PG) I The therapeutic effects of ONO-1301 against liver damage, fibrosis, and occurrence of liver tumors were evaluated using melanocortin 4 receptor-deficient (Mc4r-KO) NASH model mice. The effects of ONO-1301 against macrophages, hepatic stellate cells, and endothelial cells were also evaluated in vitro. ONO-1301 ameliorated liver damage and fibrosis progression, was effective regardless of NASH status, and suppressed the occurrence of liver tumors in Mc4r-KO NASH model mice. In the in vitro study, ONO-1301 suppressed LPS-induced inflammatory responses in cultured macrophages, suppressed hepatic stellate cell (HSC) activation, upregulated vascular endothelial growth factor (VEGF) expression in HSCs, and upregulated hepatocyte growth factor (HGF) and VEGF expression in endothelial cells. The results of our study highlight the potential of ONO-1301 to reverse the progression and prevent the occurrence of liver tumors in NASH using in vivo and in vitro models. ONO-1301 is a multidirectional drug that can play a key role in various pathways and can be further analyzed for use as a new drug candidate against NASH.
Sections du résumé
BACKGROUND
BACKGROUND
ONO-1301 is a novel long-lasting prostaglandin (PG) I
METHODS
METHODS
The therapeutic effects of ONO-1301 against liver damage, fibrosis, and occurrence of liver tumors were evaluated using melanocortin 4 receptor-deficient (Mc4r-KO) NASH model mice. The effects of ONO-1301 against macrophages, hepatic stellate cells, and endothelial cells were also evaluated in vitro.
RESULTS
RESULTS
ONO-1301 ameliorated liver damage and fibrosis progression, was effective regardless of NASH status, and suppressed the occurrence of liver tumors in Mc4r-KO NASH model mice. In the in vitro study, ONO-1301 suppressed LPS-induced inflammatory responses in cultured macrophages, suppressed hepatic stellate cell (HSC) activation, upregulated vascular endothelial growth factor (VEGF) expression in HSCs, and upregulated hepatocyte growth factor (HGF) and VEGF expression in endothelial cells.
CONCLUSIONS
CONCLUSIONS
The results of our study highlight the potential of ONO-1301 to reverse the progression and prevent the occurrence of liver tumors in NASH using in vivo and in vitro models. ONO-1301 is a multidirectional drug that can play a key role in various pathways and can be further analyzed for use as a new drug candidate against NASH.
Identifiants
pubmed: 35101153
doi: 10.1186/s41232-021-00191-6
pii: 10.1186/s41232-021-00191-6
pmc: PMC8805395
doi:
Types de publication
Journal Article
Langues
eng
Pagination
3Informations de copyright
© 2022. The Author(s).
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