Compensatory paracrine mechanisms that define the urothelial response to injury in partial bladder outlet obstruction.
Compensatory paracrine mechanisms that define the urothelial response to injury in partial bladder outlet obstruction.
复制标题
DOI：
10.1152/ajprenal.00006.2007
复制
发表时间：
2007-10
期刊：
影响因子：
--
通讯作者：
T. Lendvay;Robert Sweet;C. Han;T. Soygur;Jang-Fang Cheng;J. C. Plaire;J. Charleston;L. B. Charleston;Shelly Bagai;K. Cochrane;E. Rubio;J. Bassuk
中科院分区：
文献类型：
--
作者：
T. Lendvay;Robert Sweet;C. Han;T. Soygur;Jang-Fang Cheng;J. C. Plaire;J. Charleston;L. B. Charleston;Shelly Bagai;K. Cochrane;E. Rubio;J. Bassuk
影响下尿路的疾病和病症是性健康功能障碍、失禁、感染和肾衰竭的主要原因。膀胱上皮衬里的生长、分化和修复部分地由成纤维细胞生长因子（FGF）-7和-10经由源自间充质（固有层）并靶向移行上皮（尿道上皮）内的FGF-7和-10的受体的旁分泌级联调节。FGF-7基因位于15号染色体上的15 q15-q21.1位点，4个外显子产生3.852-kb的mRNA。预测定位于9号染色体的5个重复的FGF-7基因序列不产生功能性蛋白质产物，从而验证了FGF-7缺失小鼠作为实验模型的用途。重组FGF-7和-10在体外诱导人尿路上皮细胞增殖，在体内诱导野生型和FGF-7缺失小鼠的移行上皮细胞增殖。为了确定在膀胱对损伤的反应期间诱导尿路上皮细胞增殖依赖于FGF-7的程度，开发了部分膀胱出口梗阻的动物模型。无偏体视学用于测量野生型和FGF-7缺失小鼠的阻塞组之间的增殖尿路上皮细胞的百分比。体视学分析表明，两组之间不存在统计学显著性差异，表明FGF-7对部分出口梗阻时的尿路上皮细胞增殖不是必需的。相反，在阻塞性FGF-7缺失组中观察到FGF-10表达的显著增加，表明在该模型中起作用的代偿途径导致尿路上皮修复。
Diseases and conditions affecting the lower urinary tract are a leading cause of dysfunctional sexual health, incontinence, infection, and kidney failure. The growth, differentiation, and repair of the bladder's epithelial lining are regulated, in part, by fibroblast growth factor (FGF)-7 and -10 via a paracrine cascade originating in the mesenchyme (lamina propria) and targeting the receptor for FGF-7 and -10 within the transitional epithelium (urothelium). The FGF-7 gene is located at the 15q15-q21.1 locus on chromosome 15 and four exons generate a 3.852-kb mRNA. Five duplicated FGF-7 gene sequences that localized to chromosome 9 were predicted not to generate functional protein products, thus validating the use of FGF-7-null mice as an experimental model. Recombinant FGF-7 and -10 induced proliferation of human urothelial cells in vitro and transitional epithelium of wild-type and FGF-7-null mice in vivo. To determine the extent that induction of urothelial cell proliferation during the bladder response to injury is dependent on FGF-7, an animal model of partial bladder outlet obstruction was developed. Unbiased stereology was used to measure the percentage of proliferating urothelial cells between obstructed groups of wild-type and FGF-7-null mice. The stereological analysis indicated that a statistical significant difference did not exist between the two groups, suggesting that FGF-7 is not essential for urothelial cell proliferation in response to partial outlet obstruction. In contrast, a significant increase in FGF-10 expression was observed in the obstructed FGF-7-null group, indicating that the compensatory pathway that functions in this model results in urothelial repair.