iRhom2 inhibits bile duct obstruction-induced liver fibrosis.
ADAM17 Protein
/ genetics
Animals
Anti-Inflammatory Agents, Non-Steroidal
/ pharmacology
Bile Ducts
/ surgery
Carrier Proteins
/ genetics
Cells, Cultured
Cholestasis
/ genetics
Etanercept
/ pharmacology
Gene Expression Regulation
Hepatic Stellate Cells
/ drug effects
Humans
Ligation
Liver Cirrhosis
/ genetics
Male
Mice, Inbred C57BL
Mice, Knockout
Receptors, Tumor Necrosis Factor, Type I
/ genetics
Receptors, Tumor Necrosis Factor, Type II
/ genetics
Signal Transduction
/ drug effects
Journal
Science signaling
ISSN: 1937-9145
Titre abrégé: Sci Signal
Pays: United States
ID NLM: 101465400
Informations de publication
Date de publication:
29 10 2019
29 10 2019
Historique:
entrez:
31
10
2019
pubmed:
31
10
2019
medline:
18
8
2020
Statut:
epublish
Résumé
Chronic liver disease can induce prolonged activation of hepatic stellate cells, which may result in liver fibrosis. Inactive rhomboid protein 2 (iRhom2) is required for the maturation of A disintegrin and metalloprotease 17 (ADAM17, also called TACE), which is responsible for the cleavage of membrane-bound tumor necrosis factor-α (TNF-α) and its receptors (TNFRs). Here, using the murine bile duct ligation (BDL) model, we showed that the abundance of iRhom2 and activation of ADAM17 increased during liver fibrosis. Consistent with this, concentrations of ADAM17 substrates were increased in plasma samples from mice after BDL and in patients suffering from liver cirrhosis. We observed increased liver fibrosis, accelerated disease progression, and an increase in activated stellate cells after BDL in mice lacking iRhom2 (
Identifiants
pubmed: 31662486
pii: 12/605/eaax1194
doi: 10.1126/scisignal.aax1194
pii:
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
Carrier Proteins
0
Receptors, Tumor Necrosis Factor, Type I
0
Receptors, Tumor Necrosis Factor, Type II
0
iRhom2 protein, mouse
0
ADAM17 Protein
EC 3.4.24.86
Etanercept
OP401G7OJC
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.