MP28-07 PACE MAKER CELLS OF SPONTANEOUS ACTIVITIES ARE DOMINANTLY EXPRESSED IN SEROSA SIDE IN BLADDER OUTLET OBSTRUCTION MODEL

INTRODUCTION AND OBJECTIVE: Recently, PDGFRα+ but c-kit negative interstitial cells have been described in bladder wall as a new candidate of pace maker cells but still under controversial. The aim of this study is to clarify the pathological modification of probable pace maker cells of overactive bladder using bladder outlet obstruction (BOO) mouse. METHODS: Male C57/BL6J mice, 6-8 weeks old, were used and allocated into 2 groups. BOO and Sham were created with or without the placement of metal ring (Φ:1mm), respectively. After surgery, rearing for 10 weeks, then the urination dynamics (number of urination, micturition volume, drinking water) were observed for 2 days in metabolic cages. Accordingly, we performed cystometry. Finally taken mice bladder tissue was performed by Q-PCR, immunostaining methods. Data are presented as mean ± S.E. P value < 0.05 (*), < 0.01 (**) was considered to indicate statistical significance by student t-test. RESULTS: In micturition reflex, the number of urination per day significantly increased (13.5 ± 1.4 times vs. 7.5 ± 0.5 times; P < 0.001, N = 5) in BOO compared to sham. The daily urination volume and voiding volume were significantly decreased in BOO compared to sham (1.1 ± 0.1 ml vs. 1.9 ± 0.2 ml, 123.9 ± 3.2 μl vs. 324.3 ± 4.0 μl; P < 0.01, N = 5, respectively). In cystometry, BOO mice’s non-voiding contractions were significantly increased. In BOO, mRNA expression of c-kit, CD34 and PDGFRα was significantly elevated, however interestingly immunostaining indicated not only significant reduction of PDGFRα+ cells (9.5 ± 0.7 % vs. 14.5 ± 0.7 %; P < 0.01, N = 4) but also double positive (CD34+ and PDGFRα+) cells were dominantly expressed in serosa side but not interstitial layer in BOO model. CONCLUSIONS: BOO model mice are firstly established as overactive bladder using metal rings obviously resulting from the significant differences in voluntarily voiding behavior and various parameters from cystometry. BOO model reduced PDGFRα+ cells despite of its mRNA expression increase. This study revolutionarily demonstrated that double positive (CD34+ and PDGFRα+) cells (presumably pace maker cells) in urinary bladder were increased in serosa side but not interstitial layer in BOO model.Source of Funding: There is no disclosure.