FGF-18, a novel member of the fibroblast growth factor family, stimulates hepatic and intestinal proliferation

被引:120
作者
Hu, MCT
Qiu, WR
Wang, YP
Hill, D
Ring, BD
Scully, S
Bolon, B
DeRose, M
Luethy, R
Simonet, WS
Arakawa, T
Danilenko, DM
机构
[1] Amgen Inc, Dept Cell Biol, Thousand Oaks, CA 91320 USA
[2] Amgen Inc, Dept Pathol, Thousand Oaks, CA 91320 USA
[3] Amgen Inc, Dept Mol Genet, Thousand Oaks, CA 91320 USA
[4] Amgen Inc, Dept Computat Biol, Thousand Oaks, CA 91320 USA
[5] Amgen Inc, Dept Prot Chem, Thousand Oaks, CA 91320 USA
关键词
D O I
10.1128/MCB.18.10.6063
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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收藏
页码:6063 / 6074
页数:12
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