Fibroblast Growth Factor-10 Is a Mitogen for Urothelial Cells

• Published in: The Journal of biological chemistry 2002-06, Vol.277 (26), p.23828-23837
• Main Authors: Bagai, Shelly, Rubio, Eric, Cheng, Jang-Fang, Sweet, Robert, Thomas, Regi, Fuchs, Elaine, Grady, Richard, Mitchell, Michael, Bassuk, James A.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Amino Acid Sequence; ANIMAL CELLS; Animals; BASIC BIOLOGICAL SCIENCES; CELL NUCLEI; CHROMOSOMES; DNA - biosynthesis; DNA, Complementary - chemistry; DNA, Complementary - isolation & purification; EPITHELIUM; Escherichia coli - genetics; Fibroblast Growth Factor 10; Fibroblast Growth Factors - chemistry; Fibroblast Growth Factors - genetics; Fibroblast Growth Factors - physiology; FIBROBLASTS; GROWTH FACTORS; Humans; IN VITRO; IN VIVO; IN-SITU HYBRIDIZATION; MICE; Mice, Inbred C57BL; MITOGENS; Mitogens - physiology; Molecular Sequence Data; NUCLEAR DISARMAMENT, SAFEGUARDS, AND PHYSICAL PROTECTION; PHENOTYPE; PHOSPHORYLATION; PROLIFERATION; Recombinant Proteins - biosynthesis; Recombinant Proteins - isolation & purification; Recombinant Proteins - pharmacology; RNA; RNA, Messenger - analysis; TYROSINE; Urinary Bladder - chemistry; Urinary Bladder - cytology; URINARY TRACT
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M201658200

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.