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 ? ? ?
