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The present study was designed to investigate the functional role of U\u2010II\/UT signaling in cyclophosphamide (CYP)\u2010induced cystitis. A total of 60 female rats were randomly divided into the control and CYP\u2010treated groups. Intraperitoneal injection of CYP successfully induced cystitis in rats of the CYP\u2010treated group. The protein and mRNA expression levels of U\u2010II and UT were significantly enhanced in rat bladder tissues of the CYP\u2010treated group. Furthermore, the results of the immunofluorescence staining analysis demonstrated that CYP treatment apparently increased the expression levels of UT in the urothelium layer, detrusor smooth muscle, and bladder interstitial Cajal\u2010like cells. The selective antagonist of UT, SB657510 (10\u00a0\u03bcm), significantly suppressed the CYP\u2010induced increase in the spontaneous contractions of muscle strips and ameliorated the bladder hyperactivity of CYP\u2010treated rats. Moreover, CYP treatment significantly increased the protein expression levels of Ras homolog family member (Rho) A and Rho\u2010associated protein kinase 2 in rat bladder tissues. Following pretreatment with the Rho\u2010kinase inhibitor Y\u201027632 (10\u00a0\u03bcm), the inhibitory effects of SB657510 (10\u00a0\u03bcm) on the spontaneous contractions of muscle strips were eliminated. In conclusion, the results of the present study suggested that activation of U\u2010II\/UT signaling promoted the development of cystitis\u2010associated\u2010bladder hyperactivity by targeting the RhoA\/Rho\u2010kinase pathway, indicating that the U\u2010II\/UT signaling could serve as a novel target for the treatment of interstitial cystitis\/bladder pain syndrome.<\/jats:p>","DOI":"10.1002\/kjm2.12569","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T09:27:05Z","timestamp":1656494825000},"page":"879-888","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Inhibition of <scp>U\u2010II<\/scp>\/<scp>UT<\/scp> signaling ameliorates cystitis\u2010associated bladder hyperactivity by targeting the <scp>RhoA<\/scp>\/Rho\u2010kinase pathway"],"prefix":"10.1002","volume":"38","author":[{"given":"Qian","family":"Liu","sequence":"first","affiliation":[{"name":"Clinical Medicine Postdoctoral 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