Expression of fibroblast growth factor-5 by bovine choroidal endothelial cells in vitro. 1997

M A Keithahn, and A E Aotaki-Keen, and S A Schneeberger, and L M Hjelmeland, and L S Morse
Department of Ophthalmology, University of California, Davis, Sacramento 95816, USA.

OBJECTIVE To demonstrate the expression of fibroblast growth factor-5 (FGF-5) by bovine choroidal microvascular endothelial (BCME) cells and to investigate its possible role as an autocrine mitogen in these cells. METHODS Expression of FGF-5 by BCME cells was studied by a combination of Northern and Western blot analyses. Total RNA was isolated from BCME cultures at passages 5 through 8 and analyzed by Northern blot analysis for the presence of FGF-5 transcripts, using a 1-kb human complemetary DNA. Slot-blot analysis was performed to determine possible cross-reactivity between this probe and acidic and basic FGFs of human and bovine species. A previously characterized antibody directed against the aminoterminus of the human FGF-5 sequence was used in Western blot analyses to identify immunoreactive proteins released by BCME cells into the medium. Finally, the mitogenic activity of human recombinant FGF-5 on a variety of cell types was evaluated, using a cellular proliferation assay. RESULTS Northern blot analysis provided evidence for the expression of two major FGF-5 transcripts at 4 kb and 3 kb and two minor transcripts at 2.2 kb and 1.7 kb. A single immunoreactive protein with a molecular weight of 34 kDa was identified by Western blot analysis of conditioned media. In cellular proliferation assays, human recombinant FGF-5 was not mitogenic in BCME cells but exhibited an approximate ED50 of 1.8 to 3.7 nM in BALB/c3T3 fibroblasts. This ED50 was within the range reported by the manufacturer, using a thymidine incorporation assay and a similar embryonic fibroblast cell line. Fibroblast growth factor-5 also stimulated proliferation of human retinal pigment epithelial cells. CONCLUSIONS Bovine choroidal microvascular endothelial cells exhibit expression in vitro of FGF-5 at the messenger RNA and protein levels. Perivascular and endothelial cell staining for FGF-5 seen previously in choroidal neovascular membranes may therefore arise from expression by choroidal endothelial cells. Because nonglycosylated recombinant FGF-5 does not appear to be a mitogen in BCME cells in vitro, it is reasonable to question its role as an autocrine mitogen in vivo. Fibroblast growth factor-5 may instead be serving paracrine roles in the stimulation of fibroblasts and retinal pigment epithelial cells during the formation of choroidal neovascular membranes. Studies with fully glycosylated recombinant FGF-5 will be required, however, to assess the biologic activity of this member of the FGF gene family.

UI MeSH Term Description Entries
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D010857 Pigment Epithelium of Eye The layer of pigment-containing epithelial cells in the RETINA; the CILIARY BODY; and the IRIS in the eye. Eye Pigment Epithelium
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002829 Choroid The thin, highly vascular membrane covering most of the posterior of the eye between the RETINA and SCLERA. Choriocapillaris,Haller Layer,Haller's Layer,Sattler Layer,Sattler's Layer,Choroids
D004591 Electrophoresis, Polyacrylamide Gel Electrophoresis in which a polyacrylamide gel is used as the diffusion medium. Polyacrylamide Gel Electrophoresis,SDS-PAGE,Sodium Dodecyl Sulfate-PAGE,Gel Electrophoresis, Polyacrylamide,SDS PAGE,Sodium Dodecyl Sulfate PAGE,Sodium Dodecyl Sulfate-PAGEs
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D005346 Fibroblast Growth Factors A family of small polypeptide growth factors that share several common features including a strong affinity for HEPARIN, and a central barrel-shaped core region of 140 amino acids that is highly homologous between family members. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family. DNA Synthesis Factor,Fibroblast Growth Factor,Fibroblast Growth Regulatory Factor,Growth Factor, Fibroblast,Growth Factors, Fibroblast
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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