Fibroblast growth factor receptor 3 in hepatocytes protects from toxin-induced liver injury and fibrosis.
Biological sciences
cell biology
molecular biology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
22 Oct 2021
22 Oct 2021
Historique:
received:
16
07
2021
revised:
21
08
2021
accepted:
14
09
2021
entrez:
14
10
2021
pubmed:
15
10
2021
medline:
15
10
2021
Statut:
epublish
Résumé
The liver's remarkable regenerative capacity is orchestrated by several growth factors and cytokines. Fibroblast growth factor receptor 3 (Fgfr3) is frequently overexpressed in hepatocellular carcinoma and promotes cancer aggressiveness, whereas its role in liver homeostasis, repair and regeneration is unknown. We show here that Fgfr3 is expressed by hepatocytes in the healthy liver. Its major ligand, Fgf9, is mainly expressed by non-parenchymal cells and upregulated upon injury. Mice lacking Fgfr3 in hepatocytes exhibit increased tissue necrosis after acute toxin treatment and more excessive fibrosis after long-term injury. This was not a consequence of immunological alterations in the non-injured liver as revealed by comprehensive flow cytometry analysis. Rather, loss of Fgfr3 altered the expression of metabolic and pro-fibrotic genes in hepatocytes. These results identify a paracrine Fgf9-Fgfr3 signaling pathway that protects from toxin-induced cell death and the resulting liver fibrosis and suggests a potential use of FGFR3 ligands for therapeutic purposes.
Identifiants
pubmed: 34646985
doi: 10.1016/j.isci.2021.103143
pii: S2589-0042(21)01111-1
pmc: PMC8497853
doi:
Types de publication
Journal Article
Langues
eng
Pagination
103143Informations de copyright
© 2021 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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