Role of CC chemokine receptor 9 in the progression of murine and human non-alcoholic steatohepatitis.
Adult
Aged
Animals
Carcinoma, Hepatocellular
/ complications
Case-Control Studies
Chemokines, CC
/ blood
Diet, High-Fat
/ adverse effects
Disease Models, Animal
Disease Progression
Female
Hepatic Stellate Cells
/ metabolism
Humans
Liver
/ pathology
Liver Neoplasms
/ complications
Macrophages
/ metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Non-alcoholic Fatty Liver Disease
/ blood
Receptors, CCR
/ antagonists & inhibitors
Sulfonamides
/ administration & dosage
Treatment Outcome
CCL25/TECK
CCR9 antagonist
Hepatic stellate cell
Hepatocellular carcinoma
Liver fibrosis
NAFLD
NASH
Journal
Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
25
12
2019
revised:
07
09
2020
accepted:
28
09
2020
pubmed:
11
10
2020
medline:
21
1
2022
entrez:
10
10
2020
Statut:
ppublish
Résumé
The number of patients with non-alcoholic steatohepatitis (NASH) is increasing globally. Recently, specific chemokine receptors have garnered interest as therapeutic targets in NASH. This is the first report to examine the role of the C-C chemokine receptor 9 (CCR9)/C-C chemokine receptor ligand 25 (CCL25) axis, and to reveal its therapeutic potential in NASH. Patients with biopsy-proven non-alcoholic liver disease (NAFLD) were recruited and their serum and hepatic chemokine expression was examined. Furthermore, wild-type (WT) and Ccr9 Serum CCL25, and hepatic CCR9 and CCL25 expression levels were increased in patients with NASH compared to healthy volunteers. Furthermore, Ccr9 These results highlight the role of the CCR9/CCL25 axis on macrophage recruitment and fibrosis formation in a murine NASH model, providing new insights into therapeutic strategies for NASH. Herein, we show that a specific chemokine axis involving a receptor (CCR9) and its ligand (CCL25) contributes to the progression of non-alcoholic steatohepatitis and carcinogenesis in humans and mice. Furthermore, treatment with a CCR9 antagonist ameliorates the development of steatohepatitis and holds promise for the treatment of patients with non-alcoholic steatohepatitis.
Sections du résumé
BACKGROUND & AIMS
The number of patients with non-alcoholic steatohepatitis (NASH) is increasing globally. Recently, specific chemokine receptors have garnered interest as therapeutic targets in NASH. This is the first report to examine the role of the C-C chemokine receptor 9 (CCR9)/C-C chemokine receptor ligand 25 (CCL25) axis, and to reveal its therapeutic potential in NASH.
METHODS
Patients with biopsy-proven non-alcoholic liver disease (NAFLD) were recruited and their serum and hepatic chemokine expression was examined. Furthermore, wild-type (WT) and Ccr9
RESULTS
Serum CCL25, and hepatic CCR9 and CCL25 expression levels were increased in patients with NASH compared to healthy volunteers. Furthermore, Ccr9
CONCLUSIONS
These results highlight the role of the CCR9/CCL25 axis on macrophage recruitment and fibrosis formation in a murine NASH model, providing new insights into therapeutic strategies for NASH.
LAY SUMMARY
Herein, we show that a specific chemokine axis involving a receptor (CCR9) and its ligand (CCL25) contributes to the progression of non-alcoholic steatohepatitis and carcinogenesis in humans and mice. Furthermore, treatment with a CCR9 antagonist ameliorates the development of steatohepatitis and holds promise for the treatment of patients with non-alcoholic steatohepatitis.
Identifiants
pubmed: 33038434
pii: S0168-8278(20)33677-1
doi: 10.1016/j.jhep.2020.09.033
pii:
doi:
Substances chimiques
CC chemokine receptor 9
0
CCL25 protein, human
0
CCX282-B
0
Ccl25 protein, mouse
0
Chemokines, CC
0
Receptors, CCR
0
Sulfonamides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
511-521Informations 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.