FGF-10 and its receptor exhibit bidirectional paracrine targeting to urothelial and smooth muscle cells in the lower urinary tract.
FGF-10 and its receptor exhibit bidirectional paracrine targeting to urothelial and smooth muscle cells in the lower urinary tract.
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DOI：
10.1152/ajprenal.00025.2006
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发表时间：
2006-08
期刊：
影响因子：
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通讯作者：
Dianzhong Zhang;Jeffrey Kosman;Nicole Carmean;R. Grady;J. Bassuk
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文献类型：
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作者：
Dianzhong Zhang;Jeffrey Kosman;Nicole Carmean;R. Grady;J. Bassuk
控制尿路上皮组织的再生特性将极大地帮助临床医生管理尿路疾病和病症。成纤维细胞生长因子10（FGF-10）是一种促分裂原，特别有希望作为尿路上皮损伤的蛋白质治疗。在人尿路上皮细胞培养模型和下尿路组织的固定切片中研究了FGF-10及其受体的空间合成、转运、靶向和机制途径。FGF-10的合成仅限于间充质成纤维细胞，分泌的FGF-10表现出旁分泌转运到两个近端位点，移行上皮和平滑肌细胞束，这两者也是FGF-10受体合成的唯一位点。在体外向静止的尿路上皮细胞中加入重组FGF-10足以刺激DNA合成。这种刺激是通过一个途径独立的表皮生长因子受体途径。去卷积，光和透射电子显微镜研究捕获FGF-10及其受体与尿路上皮细胞表面，在细胞质中，并在细胞核内，观察描述的机制，在这些组织中转导促有丝分裂信号。FGF-10受体定位于浅表尿路上皮层具有临床意义，因为FGF-10的膀胱内给药可为临床医生提供一种控制膀胱疾病如间质性膀胱炎中移行上皮更新的方法。
Control of the regenerative properties of urothelial tissue would greatly aid the clinician in the management of urinary tract disease and disorders. Fibroblast growth factor 10 (FGF-10) is a mitogen which is particularly promising as a protein therapy for urothelial injury. The spatial synthesis, transport, targeting, and mechanistic pathway of FGF-10 and its receptor were studied in a human urothelial cell culture model and in fixed sections of lower urinary tract tissue. Synthesis of FGF-10 was restricted to mesenchymal fibroblasts, and secreted FGF-10 exhibited paracrine transport to two proximal sites, transitional epithelium and smooth muscle cell bundles, both of which were also the exclusive sites of FGF-10 receptor synthesis. The addition of recombinant FGF-10 to quiescent urothelial cells in vitro was sufficient to stimulate DNA synthesis. This stimulation was through a pathway independent of the epidermal growth factor receptor pathway. Deconvolution, light and transmission electron microscopic studies captured FGF-10 and its receptor in association with the urothelial cell surface, in cytoplasm, and within nuclei, observations that describe the mechanism that transduces the mitogenic signal in these tissues. Localization of the FGF-10 receptor to the superficial urothelial layer is clinically significant because intravesical administration of FGF-10 may provide the clinician a means to control the turnover of transitional epithelium in bladder disorders such as interstitial cystitis.