FGF-10 and its receptor exhibit bidirectional paracrine targeting to urothelial and smooth muscle cells in the lower urinary tract.
Control of the regenerative properties of urothelial tissue would greatly aid the clinician in the management of urinary tract disease and disorders. Fibroblast growth factor 10 (FGF-10) is a mitogen which is particularly promising as a protein therapy for urothelial injury. The spatial synthesis, transport, targeting, and mechanistic pathway of FGF-10 and its receptor were studied in a human urothelial cell culture model and in fixed sections of lower urinary tract tissue. Synthesis of FGF-10 was restricted to mesenchymal fibroblasts, and secreted FGF-10 exhibited paracrine transport to two proximal sites, transitional epithelium and smooth muscle cell bundles, both of which were also the exclusive sites of FGF-10 receptor synthesis. The addition of recombinant FGF-10 to quiescent urothelial cells in vitro was sufficient to stimulate DNA synthesis. This stimulation was through a pathway independent of the epidermal growth factor receptor pathway. Deconvolution, light and transmission electron microscopic studies captured FGF-10 and its receptor in association with the urothelial cell surface, in cytoplasm, and within nuclei, observations that describe the mechanism that transduces the mitogenic signal in these tissues. Localization of the FGF-10 receptor to the superficial urothelial layer is clinically significant because intravesical administration of FGF-10 may provide the clinician a means to control the turnover of transitional epithelium in bladder disorders such as interstitial cystitis.
Zhang
Dianzhong
D
Program in Human Urothelial Biology, Children's Hospital and Regional Medical Center, 4800 NE Sand Point Way, Mail Stop A8938, Seattle, WA 98105, USA.
Kosman
Jeffrey
J
Carmean
Nicole
N
Grady
Richard
R
Bassuk
James A
JA
D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D051526:Fibroblast Growth Factor 10 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D046529:Microscopy, Electron, Transmission; D009092:Mucous Membrane / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D019899:Paracrine Communication / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020239:Receptor Cross-Talk / Q000502:physiology; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000032:analysis / Q000235:genetics / Q000502:physiology; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014553:Urinary Tract Physiological Phenomena; D019459:Urothelium / Q000737:chemistry / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure
C496463:FGF10 protein, human; D051526:Fibroblast Growth Factor 10; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D004247:DNA; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2