Fibroblast growth factor-7 regulates stratification of the bladder urothelium
Fibroblast growth factor-7 regulates stratification of the bladder urothelium
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DOI：
10.1016/s0022-5347(05)65630-3
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发表时间：
2001-12-01
影响因子：
6.6
通讯作者：
Herzlinger, DA
中科院分区：
文献类型：
--
作者：
Tash, JA;David, SG;Herzlinger, DA
目的：调节膀胱尿路上皮组织成基底、中间和表面细胞层的细胞和分子机制仍然知之甚少。我们测试的假设，成纤维细胞生长因子（FGF）-7是必不可少的产生一个多层复层的膀胱epitheliates.Materials和方法：年龄和性别匹配的FGF-7 +/+野生型和-/- null小鼠的膀胱尿路上皮的形态和分子特征进行了评价。此外，外源性FGF-7对原代小鼠尿路上皮细胞的生长和分化的影响进行了assessment.Results：形态计量学分析表明，FGF-7无效尿路上皮细胞与野生型尿路上皮细胞相比，显着变薄。电子显微镜检查显示，null urothorax缺乏中间细胞层和分子标记物分析证实了这一观察。体外细胞培养实验表明，FGF-7调节尿路上皮细胞的生长、分化和分层。原代尿路上皮培养物保持没有FGF-7停止分裂，并表达终末分化的伞细胞的蛋白质特征。与此相反，培养物保持与外源性FGF-7含有增殖的上皮细胞的蛋白质表达模式一致的中间细胞，除了终末分化，有丝分裂后的伞细胞。重要的是，孤立的尿路上皮细胞保持与外源性FGF-7形成了一个多层的上皮细胞在vitro.Conclusions：总的来说，这些数据表明，FGF-7是必不可少的正常膀胱尿路上皮分层，特别是中间细胞层的形成。成纤维细胞生长因子-7刺激尿路上皮细胞增殖并延迟这些细胞分化为有丝分裂后的伞细胞。
Purpose: The cellular and molecular mechanisms that regulate the organization of bladder urothelium into basal, intermediate and superficial cell layers remain poorly understood. We tested the hypothesis that fibroblast growth factor (FGF)-7 is essential for generating a multilayered stratified bladder epithelium.Materials and Methods: The morphological and molecular characteristics of bladder urothelium in age and sex matched FGF-7 +/+ wild-type and -/- null mice were evaluated. In addition, the effect of exogenous FGF-7 on the growth and differentiation of primary murine urothelial cells was assessed.Results: Morphometric analyses demonstrate that FGF-7 null urothelium is markedly thinned compared with wild-type urothelium. Electron microscopy revealed that null urothelium lacks the intermediate cell layers and molecular marker analyses confirmed this observation. In vitro cell culture experiments indicated that FGF-7 regulates urothelial cell growth, differentiation and stratification. Primary urothelial cultures maintained without FGF-7 ceased to divide and expressed proteins characteristic of terminally differentiated umbrella cells. In contrast, cultures maintained with exogenous FGF-7 contained proliferating epithelial cells with protein expression patterns consistent with those of intermediate cells in addition to terminally differentiated, post-mitotic umbrella cells. Importantly, isolated urothelial cells maintained with exogenous FGF-7 formed a multilayered epithelium in vitro.Conclusions: Collectively these data indicate that FGF-7 is essential for normal bladder urothelial stratification, specifically the formation of the intermediate cell layers. Fibroblast growth factor-7 stimulates urothelial proliferation and delays the differentiation of these cells into post-mitotic umbrella cells.