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PMID: 9742123 Published · ppublish English Journal Article

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

Molecular and cellular biology ·Vol. 18 ·No. 10 ·1998-10-00 ·Pages 6063-74

Hu MC, Qiu WR, Wang YP, Hill D, Ring BD, Scully S, Bolon B, DeRose M, Luethy R, Simonet WS, Arakawa T, Danilenko DM

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.

MeSH Terms
3T3 Cells Amino Acid Sequence Animals Base Sequence Cell Division Cell Line, Transformed Cells, Cultured Cloning, Molecular DNA, Complementary Escherichia coli Fibroblast Growth Factors/genetics,metabolism Gene Expression Humans Intestine, Small/cytology Liver/cytology Mice Mice, Transgenic Molecular Sequence Data Organ Size Recombinant Fusion Proteins/genetics,metabolism Sequence Homology, Amino Acid Tissue Distribution
Chemicals
DNA, Complementary Recombinant Fusion Proteins fibroblast growth factor 18 Fibroblast Growth Factors
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Hu M C
Departments of Cell Biology, Amgen, Inc., Thousand Oaks, California 91320, USA. mhu@amgen.com
Qiu W R
Wang Y P
Hill D
Ring B D
Scully S
Bolon B
DeRose M
Luethy R
Simonet W S
Arakawa T
Danilenko D M
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.10.6063
Email
mhu@amgen.com
Published
1998-10-00
Pages
6063-74
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC109192
Subset
IM
Databases
GENBANK
AF075291, AF075292
External Links
PubMed source DOI: 10.1128/MCB.18.10.6063 PMC Full Text View journal details
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