Mechanisms of 5-HT receptor antagonists in the regulation of fibrosis in a 3D human liver spheroid model.

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
16 Jan 2024
Historique:
received: 29 08 2023
accepted: 06 12 2023
medline: 17 1 2024
pubmed: 17 1 2024
entrez: 16 1 2024
Statut: epublish

Résumé

Non-alcoholic steatohepatitis (NASH) is a major health problem leading to liver fibrosis and hepatocellular carcinoma, among other diseases, and for which there is still no approved drug treatment. Previous studies in animal models and in LX-2 cells have indicated a role for serotonin (5-HT) and 5-HT receptors in stellate cell activation and the development of NASH. In the current study, we investigated the extent to which these findings are applicable to a human NASH in vitro model consisting of human liver spheroids containing hepatocytes and non-parenchymal cells. Treatment of the spheroids with 5-HT or free fatty acids (FFA) induced fibrosis, whereas treatment of the spheroids with the 5-HT receptor antagonists ketanserin, pimavanserin, sarpogrelate, and SB269970 inhibited FFA-induced fibrosis via a reduction in stellate cell activation as determined by the expression of vimentin, TGF-β1 and COL1A1 production. siRNA-based silencing of 5-HT

Identifiants

DOI: 10.1038/s41598-023-49240-9 PMID: 38228622
pubmed: 38228622
doi: 10.1038/s41598-023-49240-9
pii: 10.1038/s41598-023-49240-9
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1396

Subventions

Organisme : European Research Council
ID : 742020
Pays : International

Informations de copyright

© 2024. The Author(s).

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Auteurs

Sara Redenšek Trampuž (S)

Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, 17177, Stockholm, Sweden.
Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia.

Sander van Riet (S)

Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, 17177, Stockholm, Sweden.

Åsa Nordling (Å)

Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, 17177, Stockholm, Sweden.

Magnus Ingelman-Sundberg (M)

Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, 17177, Stockholm, Sweden. magnus.ingelman-sundberg@ki.se.

Classifications MeSH