Proteins as Signals in Urothelial Cell Proliferation

蛋白质作为尿路上皮细胞增殖的信号

• 批准号: 7077349
• 负责人: JAMES A BASSUK
• 金额: $ 7.75万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7077349
• 关键词: Proteins; Signals; Urothelial; Cell; Proliferation

DESCRIPTION (provided by applicant): The purpose of this competing supplement is to request research support for significant expansion of the scope of "Proteins as Signals in Urothelial Cell Proliferation" (1 R01 DK62251; 04/2003 - 02/2008). Support is requested for the PI to visit the laboratory of Dr. Jennifer Southgate at the University of York, Heslington, United Kingdom, from 01/01/2006 - 03/28/2006, for the purpose of collaborative experimentation. Such experimentation is designed to better understand the mechanisms by which Fibroblast Growth Factor-10 triggers a mitogenic response within defined parameters of in vitro urothelial cell culture models. The original application contained an experimental design to develop, test, and characterize the project's reagents (e.g. recombinant proteins, antibodies, cultures, and microscopy) in a monolayer cell culture system. Next, mention was made for a future need to develop a stratified in vitro culture system where transitional epithelium would be reconstituted from proliferative, non-differentiated urothelial cells. Specific language was included to visit Dr. Southgate's laboratory in order to develop such a system. The Reviewers commented that this proposed collaboration "constituted a strength of the application". Dr. Southgate is recognized as a world leader in urothelial cell biology. Her laboratory has made remarkable progress in developing a biomimetic 3-dimensional urothelial culture model that exhibits stratified layers of basal, intermediate, and suprabasal cells; differential expression of cytokeratins and superficial tight junctions; high transepithelial electrical resistance; low diffusive permeability to urea, water, and dextran; and other characteristics of native transitional epithelium. Instead of reinventing the wheel in Seattle, a decision has been made to travel to the University of York, Heslington, UK, to expand the Aims of my funded R01. It is expected that resultant publications will strengthen the renewal of the FGF-10 (DK62251) and significantly advance the field of urothelial cell biology. Dr. Southgate and I share funded interests in urothelial dysfunction, e.g. interstitial cystitis, and our joint work is expected to lead to a better understanding of the steady-state interrelationships that involve urothelial cells, growth factors, matricellular proteins, the extracellular matrix, and the urothelial basement membrane. Advancing the study of FGF-10 is relevant because of the polypeptide's potential use as a clinical tool to treat, and ultimately cure, a variety of lower urinary tract conditions and diseases

描述（由申请人提供）：这种竞争补充剂的目的是要求研究支持“蛋白质作为尿路上皮细胞增殖中的信号”的范围的显着扩展（1 R01 DK62251; 04/2003-2003-02/2008）。要求支持PI访问英国赫斯灵顿大学詹妮弗·索斯盖特（Jennifer Southgate）博士，2006年1月1日至2006年3月28日，以进行协作实验。这种实验旨在更好地理解成纤维细胞生长因子10的机制，从而在体外尿路上皮细胞培养模型的定义参数中触发有丝分裂反应。原始应用包含一种实验设计，用于在单层细胞培养系统中开发，测试和表征项目的试剂（例如重组蛋白，抗体，培养物和显微镜）。接下来，提到未来需要开发分层的体外培养系统，在该系统中，将从增生性，非差异尿路上皮细胞中重组过渡上皮。包括特定语言来访问Southgate博士的实验室，以开发这种系统。审稿人评论说，这种提议的合作“构成了应用程序的优势”。 Southgate博士被公认为是尿路上皮细胞生物学的世界领导者。她的实验室在开发仿生的三维尿路上皮培养模型方面取得了显着的进步，该模型表现出分层的基底，中间和上质细胞。细胞角蛋白的差异表达和浅表紧密连接；高旋转电阻；对尿素，水和葡萄糖的扩散渗透性低；以及天然过渡上皮的其他特征。与其重塑西雅图的轮子，不如决定前往约克大学，英国赫斯灵顿大学，以扩大我资助的R01的目标。预计由此产生的出版物将加强FGF-10（DK62251）的更新，并显着推进尿路上皮细胞生物学领域。 Southgate博士和我分享了尿路上皮功能障碍的利益，例如间质性膀胱炎和我们的联合工作有望使稳态相互关系有更好的了解，该稳态相互关系涉及尿路上皮细胞，生长因子，基质细胞蛋白，细胞外基质和尿路上皮基底膜膜。进行FGF-10的研究是相关的