RhoA mRNA was increased after 14 days of pBOO (1.92 [+ or -] 0.16-fold, p=0.04) and treatment with mSc resulted in a significant decrease (0.45 [+ or -] 0.23 vs.
Although bladder pressures increased after pBOO, these were not significantly higher than the unobstructed animals and no change was detected with MSC treatment (Fig.
Treatment with MSC has demonstrated exciting results in many pathologic conditions and we believe our data shows similar promise with respect to pBOO. (14,15) MSCs possess significant immunomodulatory effects, promote tissue healing and regeneration, prevent apoptosis, and are pro-angiogenic.
We have previously described the inflammatory reaction that occurs after a surgically induced pBOO. We hypothesized that concomitant administration of MSC with pBOO will result in a decrease in these inflammatory mediators and that this will result in improvement of several quantifiable parameters.
Our experiment definitively demonstrated uptake of MSC into bladders after pBOO. However, we were not able to examine uptake into other organs to discern whether the MSC accumulation was a passive process or if the inflammation resulted in active recruitment of our cells.
Bladder wall hypoxia is significant after pBOO, (1,15) and we demonstrated that
(1,8) Our findings confirm the presence of ERS after 14 days of pBOO, evident by the increase in GRP78 protein levels.
(16) These findings suggest an important role of ERS after pBOO. Further work confirming a causative role may lead to novel medical preventive strategies.
RhoA (Ras homolog transforming protein member A) increased significantly after 14 days of pBOO. Activation of RhoA results in increased contractility and cytoskeletal modulation.
Hypoxia and mechanical stress, two primary factors after pBOO, have been shown to activate RhoA/ROCK.
(2,27) We detected a significant reduction in decorin and lumican after 2 weeks of pBOO, consistent with a pro-fibrotic environment and deregulated collagen assembly.
Figure 5 summarizes the changes in protein expression detected in this study, and their possible inducers, downstream effects, and interactions after pBOO.