Attenuation of bladder overactivity in KIT mutant rats

Abstract

What's known on the subject? and What does the study add? Attenuation of KIT activity in ICCs of KIT gene-deficient rat bladder may demonstrate the possibility of negatively regulating the sensory pathway of bladder hyperactivity mediated by C-fibers, suggesting that KIT could be a candidate target of medical therapy in the future. Although recent reports have suggested that KIT is a detection marker of interstitial cells (ICC)s in the urinary bladder, there are few reports that ICCs themselves play a crucial role in the control of bladder function. We identify the role of KIT in the sensory mechanisms of urinary bladder in this paper. Objective:S To investigate morphological and physiological findings in the bladder of KIT mutant (WsRCWs/Ws) rats to clarify whether the disturbance of KIT pathways affects bladder activity. To discuss the potential role of KIT-positive interstitial cells of Cajal (ICC)-like cells in the urinary bladder. Materials and methods: Reverse transcriptase-polymerase chain reaction and western blotting was used to confirm the absence of c-kit mRNA and protein in the bladders of 12-week-old WsRCWs/Ws rats. Light and transmission electron microscopy was used to identify the differences in morphological and ultrastructural characteristics of the bladder between WsRCWs/Ws and wild-type (WsRC+/+) rats. The voiding pattern of WsRCWs/Ws rats and the effects of cyclophosphamide (CYP) and protamine sulphate on bladder function were examined using cystometry. Results: In WsRC+/+ rats, c-kit mRNA and KIT protein expression were observed in the urinary bladder, while they were not detectable in WsRCWs/Ws rats. Deformation of ICC-like cells with the collapse of the organelle was not observed in the bladders of WsRCWs/Ws rats. Each cystometry variable in WsRCWs/Ws rats was similar to that in WsRC+/+ rats. The reduction in the intercontraction intervals in WsRCWs/Ws rats with chemically (CYP and protamine sulphate) induced cystitis was significantly lower than in WsRC+/+ rats (P < 0.05). Conclusion: Certain voiding disturbances might be associated with impaired KIT signalling in ICC-like cells, therefore, KIT could be a candidate target for medical therapy in the future. © 2010 BJU International.