Attenuation of bladder overactivity in KIT mutant rats

Abstract

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. 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. 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). 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.