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

MCT Hu, WR Qiu, Y Wang, D Hill, BD Ring… - … and cellular biology, 1998 - Taylor & Francis
MCT Hu, WR Qiu, Y Wang, D Hill, BD Ring, S Scully, B Bolon, M DeRose, R Luethy
Molecular and cellular biology, 1998Taylor & Francis
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 …
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.
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