title: FGF-18, a novel member of the fibroblast growth factor family, stimulates hepatic and intestinal proliferation.
abstract: The fibroblast growth factors (FGFs) play key roles in controlling tissue growth, morphogenesis, and repair in animals. We have cloned a novel member of the FGF family, designated FGF-18, that is expressed primarily in the lungs and kidneys and at lower levels in the heart, testes, spleen, skeletal muscle, and brain. Sequence comparison indicates that FGF-18 is highly conserved between humans and mice and is most homologous to FGF-8 among the FGF family members. FGF-18 has a typical signal sequence and was glycosylated and secreted when it was transfected into 293-EBNA cells. Recombinant murine FGF-18 protein (rMuFGF-18) stimulated proliferation in the fibroblast cell line NIH 3T3 in vitro in a heparan sulfate-dependent manner. To examine its biological activity in vivo, rMuFGF-18 was injected into normal mice and ectopically overexpressed in transgenic mice by using a liver-specific promoter. Injection of rMuFGF-18 induced proliferation in a wide variety of tissues, including tissues of both epithelial and mesenchymal origin. The two tissues which appeared to be the primary targets of FGF-18 were the liver and small intestine, both of which exhibited histologic evidence of proliferation and showed significant gains in organ weight following 7 (sometimes 3) days of FGF-18 treatment. Transgenic mice that overexpressed FGF-18 in the liver also exhibited an increase in liver weight and hepatocellular proliferation. These results suggest that FGF-18 is a pleiotropic growth factor that stimulates proliferation in a number of tissues, most notably the liver and small intestine.
authors.affiliation: Departments of Cell Biology, Amgen, Inc., Thousand Oaks, California 91320, USA. mhu@amgen.com
authors.forename: M C
authors.initials: MC
authors.lastname: Hu
authors.forename: W R
authors.initials: WR
authors.lastname: Qiu
authors.forename: Y P
authors.initials: YP
authors.lastname: Wang
authors.forename: D
authors.initials: D
authors.lastname: Hill
authors.forename: B D
authors.initials: BD
authors.lastname: Ring
authors.forename: S
authors.initials: S
authors.lastname: Scully
authors.forename: B
authors.initials: B
authors.lastname: Bolon
authors.forename: M
authors.initials: M
authors.lastname: DeRose
authors.forename: R
authors.initials: R
authors.lastname: Luethy
authors.forename: W S
authors.initials: WS
authors.lastname: Simonet
authors.forename: T
authors.initials: T
authors.lastname: Arakawa
authors.forename: D M
authors.initials: DM
authors.lastname: Danilenko
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004926:Escherichia coli; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007421:Intestine, Small / Q000166:cytology*; D008099:Liver / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009929:Organ Size; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
chemical_list: D018076:DNA, Complementary; D011993:Recombinant Fusion Proteins; C113569:fibroblast growth factor 18; D005346:Fibroblast Growth Factors