Fibroblast growth factor receptor signalling is crucial for liver homeostasis and regeneration.
Several growth factors have been suggested to play a crucial role in liver regeneration, but a functional proof is still missing. Since fibroblast growth factors are important for the initiation of mammalian liver development, we determined the roles of these mitogens in liver repair by targeted expression of a dominant-negative fibroblast growth factor receptor (FGFR) in hepatocytes of transgenic mice. The liver of young animals appeared histologically normal, and liver function was not obviously impaired. In aged transgenic mice, the frequency of fatty liver development was strongly increased compared to control animals. Following partial hepatectomy, transgenic mice showed markedly reduced hepatocyte proliferation because of an arrest in the late G(1) phase of the cell cycle. These data demonstrate a key role of FGFR signalling in repair after liver injury.
Steiling
Heike
H
Institute of Cell Biology, ETH Zürich, Hönggerberg, CH-8093 Zürich, Switzerland.
Wüstefeld
Torsten
T
Bugnon
Philippe
P
Brauchle
Maria
M
Fässler
Reinhard
R
Teupser
Daniel
D
Thiery
Joachim
J
Gordon
Jeffrey I
JI
Trautwein
Christian
C
Werner
Sabine
S
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division; D005234:Fatty Liver / Q000209:etiology; D016193:G1 Phase; D006498:Hepatectomy; D022781:Hepatocytes / Q000502:physiology; D006706:Homeostasis; D008099:Liver / Q000378:metabolism; D008115:Liver Regeneration / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology*
D017468:Receptors, Fibroblast Growth Factor; C496354:Fgfr2 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D001973:Bromodeoxyuridine