Fibroblast growth factor-10 is a mitogen for urothelial cells
Fibroblast growth factor-10 is a mitogen for urothelial cells
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DOI：
10.1074/jbc.m201658200
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发表时间：
2002-06-28
影响因子：
4.8
通讯作者：
Bassuk, JA
中科院分区：
文献类型：
--
作者：
Bagai, S;Rubio, E;Bassuk, JA
成纤维细胞生长因子(FGF)-10在调节尿路上皮的生长、分化和修复中起重要作用。这一过程通过旁分泌级联发生，起源于间质（固有层），并以上皮（尿路上皮）为目标。原位杂交分析表明：(1)人固有层成纤维细胞是合成FGF-10 RNA的细胞类型；(2)FGF-10基因位于5号染色体5p12-p13位点。重组人FGF-10制剂在体外可诱导人尿路上皮细胞增殖，在体内可诱导野生型和fgf7缺失小鼠的移行上皮细胞增殖。对人类细胞的机制研究表明，FGF-10的作用有两种模式：rFGF-10转位进入尿路上皮细胞核和（ii）信号级联，始于肝素依赖的表面跨膜受体酪氨酸残基磷酸化。正常的尿路上皮表型，即静止的表型，被认为是由FGF-10的可忽略不计的水平来表征的。在增殖期，尿路上皮细胞表面和/或细胞核内的FGF-10水平升高。了解FGF-10如何与这些其他过程一起工作将有助于更好地管理膀胱和泌尿道的许多疾病。
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.