Role of PNPLA3 in Hepatic Stellate Cells and Hepatic Cellular Crosstalk.
hepatic stellate cells (HSCs): patatin‐like phospholipase domain containing 3 (PNPLA3)
liver cirrhosis
liver fibrosis
liver inflammation
metabolic dysfunction‐associated steatohepatitis (MASH)
metabolic dysfunction‐associated steatotic liver disease (MASLD)
nuclear receptors (NR)
Journal
Liver international : official journal of the International Association for the Study of the Liver
ISSN: 1478-3231
Titre abrégé: Liver Int
Pays: United States
ID NLM: 101160857
Informations de publication
Date de publication:
12 Oct 2024
12 Oct 2024
Historique:
revised:
16
09
2024
received:
29
08
2024
accepted:
17
09
2024
medline:
12
10
2024
pubmed:
12
10
2024
entrez:
12
10
2024
Statut:
aheadofprint
Résumé
Since its discovery, the patatin-like phospholipase domain containing 3 (PNPLA3) (rs738409 C>G p.I148M) variant has been studied extensively to unravel its molecular function. Although several studies proved a causal relationship between the PNPLA3 I148M variant and MASLD development and particularly fibrosis, the pathological mechanisms promoting this phenotype have not yet been fully clarified. We summarise the latest data regarding the PNPLA3 I148M variant in hepatic stellate cells (HSCs) activation and macrophage biology or the path to inflammation-induced fibrosis. Elegant but contradictory studies have ascribed PNPLA3 a hydrolase or an acyltransferase function. The PNPLA3 I148M results in hepatic lipid accumulation, which predisposes the hepatocyte to lipotoxicity and lipo-apoptosis, producing DAMPs, cytokines and chemokines leading to recruitment and activation of macrophages and HSCs, propagating fibrosis. Recent studies showed that the PNPLA3 I148M variant alters HSCs biology via attenuation of PPARγ, AP-1, LXRα and TGFβ activity and signalling. The advent of refined techniques in isolating HSCs has made PNPLA3's direct role in HSCs for liver fibrosis development more apparent. However, many other mechanisms still need detailed investigations.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Institute for Health Research University College London Hospitals - Biomedical Research Centre
ID : BRC648.III.KR.101350
Organisme : Austrian Science Fund
ID : SFB F73 [F7301]
Organisme : Medical Scientific Fund of the Mayor of the City of Vienna
ID : 21088
Informations de copyright
© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.
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