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

Thomas S. Lendvay, Robert Sweet, Chang Hee Han, Tarkan Soygur, Jan Fan Cheng, J. Chadwick Plaire, Jay S. Charleston, Lynne B. Charleston, Shelly Bagai, Kimberly Cochrane, Eric Rubio, James A. Bassuk

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)F1147-F1156
JournalAmerican Journal of Physiology - Renal Physiology
Volume293
Issue number4
DOIs
StatePublished - Oct 2007

Keywords

  • Fibroblast growth factor-10
  • Fibroblast growth factor-7
  • Keratinocyte growth factor
  • Stereology
  • Transitional epithelium

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