Bladder stromal loss of transforming growth factor receptor II decreases fibrosis after bladder obstruction

G Anumanthan, ST Tanaka, CM Adams… - The Journal of …, 2009 - auajournals.org
G Anumanthan, ST Tanaka, CM Adams, JC Thomas, ML Wills, MC Adams, SW Hayward
The Journal of urology, 2009auajournals.org
Purpose: Transforming growth factor-β is a potent stimulator of extracellular matrix
production. Several studies show that loss of transforming growth factor-β signaling
decreases kidney, liver and lung fibrosis. However, the role of transforming growth factor-β
signaling in bladder fibrosis is not entirely understood. We investigated the effect of stromal
loss of such signaling in mice after partial bladder outlet obstruction. Materials and Methods:
We performed partial bladder outlet obstruction by urethral ligation in 5-week-old female …
Purpose
Transforming growth factor-β is a potent stimulator of extracellular matrix production. Several studies show that loss of transforming growth factor-β signaling decreases kidney, liver and lung fibrosis. However, the role of transforming growth factor-β signaling in bladder fibrosis is not entirely understood. We investigated the effect of stromal loss of such signaling in mice after partial bladder outlet obstruction.
Materials and Methods
We performed partial bladder outlet obstruction by urethral ligation in 5-week-old female Tgfbr2colTKO mice. These mice were compared to WT mice with partial bladder outlet obstruction and to WT nonobstructed controls. After 4 weeks and before sacrifice urodynamics were performed. Bladder tissue was harvested, and p-Smad2 and collagen (Masson's trichrome) staining were performed.
Results
Bladder compliance was increased in partially obstructed Tgfbr2colTKO mice and decreased in partially obstructed WT mice. The latter had increased smooth muscle hypertrophy and increased collagen deposition between smooth muscle bundles compared to those in Tgfbr2colTKO mice and nonobstructed controls. Transforming growth factor-β responsive collagen promoter activity was significantly decreased in Tgfbr2 knockout bladder stromal cells vs WT stromal cells.
Conclusions
Stromal loss of transforming growth factor-β signaling decreased collagen deposition after partial bladder outlet obstruction. In contrast to collagen production by recruited macrophages, stromal transforming growth factor-β signaling appears to be the primary source of fibrosis after partial bladder outlet obstruction. These findings further support the hypothesis that manipulating transforming growth factor-β signaling in bladder stromal cells would provide a future avenue for neuropathic bladder and bladder fibrosis treatment.
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