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DEVELOPMENTAL REGULATORS YAP/TAZ IN THE BLADDER RESPONSE TO
INJURY.
Martin SIDLER
1
, Karen AITKEN
2
, Jia-Xin JIANG
2
and Darius BAGLI
3
1) University of Toronto, Institute of Medical Sciences, Toronto, CANADA - 2) Research Institute, Sickkids Hospital,
Developmental and Stem Cell Biology, Toronto, CANADA - 3) Sickkids Hospital, Division of Urology, Department of
Surgery, Toronto, CANADA
PURPOSE
In muscle cells, YAP or TAZ localization to the nucleus can promote either growth or differentiation. While YAP has been
studied developmentally in the urinary tract, little is known concerning the regulation of YAP or TAZ and its downstream
partners in models of mechanical stress in bladder smooth muscle. PURPOSE: To examine the regulation of YAP and TAZ
transcription and localization during bladder mechanical strain. HYPOTHESIS: YAP and TAZ and downstream targets are
differentially regulated during mechanical strain injury.
MATERIAL AND METHODS
For in vitro stretch, neonatal rat bladder smooth muscle cells (BSMC) were exposed to 0 or 5% elongation in vitro. To
create partial bladder outlet obstruction (PBO) in Sprague-Dawley female rats (n=8), a silk suture was tied around a 0.9
mm steel rod. The rod was removed with suture remaining in place. Controls included sham-operated rats (n=6). QPCR
was performed for key YAP/TAZ pathway members (MST, YAP, TAZ, TEADs 1-4) and YAP downstream targets. YAP/TAZ
nuclear localization, which indicates activation, was studied by immunofluorescence.
RESULTS
During mechanical strain expression of YAP mRNA was maintained, while TAZ mRNA expression was significantly
decreased (p<0.05). A 27-fold reduction (p<0.05) in MST1 mRNA expression during mechanical strain was consistent
with an observed increase YAP protein nuclear localization (p<0.03). TAZ was also downregulated during PBO (p<0.01).
YAP nuclear localization was correlated with increased hypertrophy, but YAP mRNA did not change. Many transcriptional
targets of YAP/TAZ were upregulated during mechanical strain and obstruction (p<0.03).
CONCLUSIONS
The YAP-TAZ complex responds to both cell strain and PBO in vivo with associated SMC growth and hypertrophy, using
both transcriptional and post-translational mechanisms.