Fibroblast growth factor-10 is a mitogen for urothelial cells

被引:47
作者
Bagai, S
Rubio, E
Cheng, JF
Sweet, R
Thomas, R
Fuchs, E
Grady, R
Mitchell, M
Bassuk, JA
机构
[1] Univ Washington, Dept Urol, Sch Med, Seattle, WA 98195 USA
[2] Univ Calif Berkeley, Lawrence Berkeley Lab, Dept Genome Sci, Berkeley, CA 94720 USA
[3] Univ Chicago, Howard Hughes Med Inst, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA
[4] Univ Washington, Childrens Hosp & Med Ctr, Div Pediat Urol, Seattle, WA 98105 USA
[5] Univ Washington, Sch Med, Dept Urol, Seattle, WA 98105 USA
关键词
D O I
10.1074/jbc.M201658200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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: M 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.
引用
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页码:23828 / 23837
页数:10
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