Fibroblast growth factor-10 is a mitogen for urothelial cells.
Fibroblast growth factor (FGF)-10 plays an important role in regulating growth, differentiation, and repair of the urothelium. This process occurs through a paracrine cascade originating in the mesenchyme (lamina propria) and targeting the epithelium (urothelium). In situ hybridization analysis demonstrated that (i) fibroblasts of the human lamina propria were the cell type that synthesized FGF-10 RNA and (ii) the FGF-10 gene is located at the 5p12-p13 locus of chromosome 5. Recombinant (r) preparations of human FGF-10 were found to induce proliferation of human urothelial cells in vitro and of transitional epithelium of wild-type and FGF7-null mice in vivo. Mechanistic studies with human cells indicated two modes of FGF-10 action: (i) translocation of rFGF-10 into urothelial cell nuclei and (ii) a signaling cascade that begins with the heparin-dependent phosphorylation of tyrosine residues of surface transmembrane receptors. The normal urothelial phenotype, that of quiescence, is proposed to be typified by negligible levels of FGF-10. During proliferative phases, levels of FGF-10 rise at the urothelial cell surface and/or within urothelial cell nuclei. An understanding of how FGF-10 works in conjunction with these other processes will lead to better management of many diseases of the bladder and urinary tract.
Bagai
Shelly
S
Department of Urology, University of Washington School of Medicine, Seattle, Washington 98195, USA.
Rubio
Eric
E
Cheng
Jang-Fang
JF
Sweet
Robert
R
Thomas
Regi
R
Fuchs
Elaine
E
Grady
Richard
R
Mitchell
Michael
M
Bassuk
James A
JA
D000595:Amino Acid Sequence; D000818:Animals; D004247:DNA / Q000096:biosynthesis; D018076:DNA, Complementary / Q000737:chemistry / Q000302:isolation & purification; D004926:Escherichia coli / Q000235:genetics; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000502:physiology*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D001743:Urinary Bladder / Q000737:chemistry / Q000166:cytology*
D018076:DNA, Complementary; C496463:FGF10 protein, human; C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D008934:Mitogens; D012333:RNA, Messenger; D011994:Recombinant Proteins; D005346:Fibroblast Growth Factors; D004247:DNA