Abstract
Partial bladder outlet obstruction (pBOO) causes considerable remodeling of the urinary bladder resulting in bladder organ hypertrophy. The serine/threonine protein kinase Akt serves as a convergent point in signaling networks and plays a critical role in cellular survival and growth. At 2 weeks after surgically induction of pBOO in rat, the phosphorylation (activation) level of the Akt isoform Akt1 was significantly increased in the urinary bladder, whereas the activity of Akt2 was not changed. In the urinary bladder with pBOO, excessive collagen deposition played a significant role in bladder hypertrophy, however, real‐time PCR showed that collagen mRNA level was not changed when compared to control. This was consistent to that the phosphorylation (activation) level of mammalian target of rapamycin (mTOR), p70S6 kinase (p70S6K), and 4E‐BP1, a protein synthesis pathway downstream of Akt1, were increased in pBOO bladder. The increases in protein synthesis also resulted in detrusor smooth muscle cellular hypertrophy examined by an increase in the relative level of α‐smooth muscle actin against nuclear protein histone H3. These results suggest that an increased protein synthesis regulated by Akt1‐mediated translational machinery may underlie pBOO‐induced bladder hypertrophy resulting from excessive collagen deposition and detrusor smooth muscle cellular hypertrophy.
Grant Funding Source: DK077917