Integrin β
Animals
Antibodies, Neutralizing
/ administration & dosage
Cell Adhesion
/ immunology
Diet, High-Fat
Disease Models, Animal
Extracellular Vesicles
/ immunology
Hepatocytes
/ immunology
Humans
Integrin beta1
/ immunology
Liver Cirrhosis
/ prevention & control
Lysophosphatidylcholines
/ pharmacology
Macrophages
/ immunology
Mice
Monocytes
/ immunology
Non-alcoholic Fatty Liver Disease
/ immunology
Adhesion
Extracellular vesicles
Fibrosis
Inflammation
Integrin α(9)
Integrin β(1)
Liver sinusoidal endothelial cells
Mass cytometry
Monocytes
NASH
Journal
Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
17
04
2019
revised:
08
07
2019
accepted:
15
07
2019
pubmed:
23
8
2019
medline:
20
3
2021
entrez:
22
8
2019
Statut:
ppublish
Résumé
Hepatic recruitment of monocyte-derived macrophages (MoMFs) contributes to the inflammatory response in non-alcoholic steatohepatitis (NASH). However, how hepatocyte lipotoxicity promotes MoMF inflammation is unclear. Here we demonstrate that lipotoxic hepatocyte-derived extracellular vesicles (LPC-EVs) are enriched with active integrin β Hepatocytes were treated with either vehicle or the toxic lipid mediator lysophosphatidylcholine (LPC); EVs were isolated from the conditioned media and subjected to proteomic analysis. C57BL/6J mice were fed a diet rich in fat, fructose, and cholesterol (FFC) to induce NASH. Mice were treated with anti-ITGβ Ingenuity® Pathway Analysis of the LPC-EV proteome indicated that ITG signaling is an overrepresented canonical pathway. Immunogold electron microscopy and nanoscale flow cytometry confirmed that LPC-EVs were enriched with activated ITGβ Lipotoxic EVs mediate monocyte adhesion to LSECs mainly through an ITGβ Herein, we report that a cell adhesion molecule termed integrin β
Sections du résumé
BACKGROUND & AIMS
Hepatic recruitment of monocyte-derived macrophages (MoMFs) contributes to the inflammatory response in non-alcoholic steatohepatitis (NASH). However, how hepatocyte lipotoxicity promotes MoMF inflammation is unclear. Here we demonstrate that lipotoxic hepatocyte-derived extracellular vesicles (LPC-EVs) are enriched with active integrin β
METHODS
Hepatocytes were treated with either vehicle or the toxic lipid mediator lysophosphatidylcholine (LPC); EVs were isolated from the conditioned media and subjected to proteomic analysis. C57BL/6J mice were fed a diet rich in fat, fructose, and cholesterol (FFC) to induce NASH. Mice were treated with anti-ITGβ
RESULTS
Ingenuity® Pathway Analysis of the LPC-EV proteome indicated that ITG signaling is an overrepresented canonical pathway. Immunogold electron microscopy and nanoscale flow cytometry confirmed that LPC-EVs were enriched with activated ITGβ
CONCLUSIONS
Lipotoxic EVs mediate monocyte adhesion to LSECs mainly through an ITGβ
LAY SUMMARY
Herein, we report that a cell adhesion molecule termed integrin β
Identifiants
pubmed: 31433301
pii: S0168-8278(19)30460-X
doi: 10.1016/j.jhep.2019.07.019
pmc: PMC6864271
mid: NIHMS1536747
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Integrin beta1
0
Itgb1 protein, mouse
0
Lysophosphatidylcholines
0
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
1193-1205Subventions
Organisme : NIDDK NIH HHS
ID : K08 DK111397
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA015083
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK084567
Pays : United States
Informations de copyright
Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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