Hepatic stellate cell activation promotes alcohol-induced steatohepatitis through Igfbp3 and SerpinA12.
Adaptor Proteins, Signal Transducing
/ metabolism
Animals
Disease Models, Animal
Fatty Liver, Alcoholic
/ complications
Fibrosis
/ etiology
Hepatic Stellate Cells
/ metabolism
Inflammation
/ metabolism
Insulin-Like Growth Factor Binding Protein 3
/ metabolism
Mice
Neuropilin-1
/ metabolism
Serine Proteinase Inhibitors
/ metabolism
Serpins
/ metabolism
Signal Transduction
Alcohol
Alcoholic hepatitis
Alcoholic liver disease
Hepatic stellate cell
Igfbp3
Insulin-like growth factor-binding protein 3
Integrin
Neuropilin-1
SerpinA12
Src-kinase
Steatohepatitis
Steatosis
Vaspin
Journal
Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
20
06
2018
revised:
23
01
2020
accepted:
01
02
2020
pubmed:
23
2
2020
medline:
6
11
2021
entrez:
23
2
2020
Statut:
ppublish
Résumé
Steatohepatitis drives fibrogenesis in alcohol-related liver disease. Recent studies have suggested that hepatic stellate cells (HSCs) may regulate the parenchymal cell injury and inflammation that precedes liver fibrosis, although the mechanism remains incompletely defined. Neuropilin-1 (NRP-1) and synectin are membrane proteins implicated in HSC activation. In this study, we disrupted NRP-1 and synectin as models to evaluate the role of HSC activation on the development of steatohepatitis in response to alcohol feeding in mice. Mice with HSC-selective deletion of NRP (Col Col Selective deletion of NRP-1 from HSCs attenuates alcohol-induced steatohepatitis through regulation of Igfbp3 and SerpinA12 signaling. Hepatic stellate cells are known for their role in fibrosis (scarring of the liver). In this study, we describe their role in the modulation of fat deposition and inflammation in the liver, which occurs secondary to alcohol damage.
Sections du résumé
BACKGROUND & AIMS
Steatohepatitis drives fibrogenesis in alcohol-related liver disease. Recent studies have suggested that hepatic stellate cells (HSCs) may regulate the parenchymal cell injury and inflammation that precedes liver fibrosis, although the mechanism remains incompletely defined. Neuropilin-1 (NRP-1) and synectin are membrane proteins implicated in HSC activation. In this study, we disrupted NRP-1 and synectin as models to evaluate the role of HSC activation on the development of steatohepatitis in response to alcohol feeding in mice.
METHODS
Mice with HSC-selective deletion of NRP (Col
RESULTS
Col
CONCLUSION
Selective deletion of NRP-1 from HSCs attenuates alcohol-induced steatohepatitis through regulation of Igfbp3 and SerpinA12 signaling.
LAY SUMMARY
Hepatic stellate cells are known for their role in fibrosis (scarring of the liver). In this study, we describe their role in the modulation of fat deposition and inflammation in the liver, which occurs secondary to alcohol damage.
Identifiants
pubmed: 32087348
pii: S0168-8278(20)30103-3
doi: 10.1016/j.jhep.2020.02.005
pmc: PMC7305991
mid: NIHMS1571307
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Gipc1 protein, mouse
0
Insulin-Like Growth Factor Binding Protein 3
0
Serine Proteinase Inhibitors
0
Serpins
0
Neuropilin-1
144713-63-3
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
149-160Subventions
Organisme : NIAAA NIH HHS
ID : R01 AA021171
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK059615
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK117861
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK084567
Pays : United States
Organisme : NIAAA NIH HHS
ID : R37 AA021171
Pays : United States
Organisme : NIDDK NIH HHS
ID : R56 DK059615
Pays : United States
Informations de copyright
Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.
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