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This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: 293/4/F1147    most recent 00006.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lendvay, T. S. Articles by Bassuk, J. A. Search for Related Content PubMed PubMed Citation Articles by Lendvay, T. S. Articles by Bassuk, J. A.

Compensatory paracrine mechanisms that define the urothelial response to injury in partial bladder outlet obstruction

¹Program in Human Urothelial Biology, Seattle Children's Hospital Research Institute, Seattle; ²Department of Urology, University of Washington School of Medicine, Seattle; ⁴Stereotome Northwest, Issaquah, Washington; and ³Department of Genome Sciences, Ernst Orlando Lawrence Berkeley Laboratory, Berkeley, California

Submitted 3 January 2007 ; accepted in final form 21 June 2007

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.

transitional epithelium; fibroblast growth factor-7; fibroblast growth factor-10; keratinocyte growth factor; stereology