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Fgfr2 is integral for bladder mesenchyme patterning and function.

Y Ikeda1, I Zabbarova1, C M Schaefer2

  • 1Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

American Journal of Physiology. Renal Physiology
|January 6, 2017
PubMed
Summary
This summary is machine-generated.

Fibroblast growth factor receptor 2 (Fgfr2) is crucial for bladder development. Its absence in mice leads to abnormal bladder mesenchyme, causing muscle loss and impaired function due to altered hedgehog signaling.

Keywords:
bladder developmentbladder dysfunctionfibroblast growth factor receptor 2

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Area of Science:

  • Urology
  • Developmental Biology
  • Genetics

Background:

  • Urothelial signals, like sonic hedgehog (Shh), influence bladder mesenchyme differentiation.
  • Fibroblast growth factor receptor 2 (Fgfr2) is known to be essential for kidney and ureter mesenchymal development.

Purpose of the Study:

  • To investigate the specific role of Fgfr2 within the bladder mesenchyme during development.
  • To determine the impact of Fgfr2 deletion on bladder structure and function.

Main Methods:

  • Utilized Tbx18cre mice for targeted deletion of Fgfr2 in bladder mesenchyme (Fgfr2-/-).
  • Employed a comprehensive suite of techniques including 3D reconstructions, molecular analyses (qPCR, in situ hybridization, immunolabeling, ELISA, immunoblotting), and functional assays (ex vivo bladder sheets, in vivo cystometry).

Main Results:

  • Fgfr2-/- bladders exhibited thin muscle layers with reduced alpha-smooth muscle actin and thickened lamina propria with increased collagen from embryonic day 16.5 onwards.
  • Progressive muscle loss and collagen deposition were observed postnatally (P1-P30).
  • Fgfr2-/- bladders showed decreased contractility, increased passive tension, and abnormal in vivo urodynamic parameters (high baseline/threshold pressures, shortened intercontractile intervals).
  • Mechanistically, Fgfr2 deletion led to enhanced hedgehog signaling, indicated by increased hedgehog activity readouts and elevated levels of hedgehog coreceptors Cdo and Boc.

Conclusions:

  • Fibroblast growth factor receptor 2 (Fgfr2) is critical for proper bladder mesenchyme patterning.
  • Fgfr2 regulates bladder development, in part, by modulating hedgehog signaling pathways.
  • Disruption of Fgfr2 in bladder mesenchyme results in significant structural and functional deficits.