{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T11:20:56Z","timestamp":1782127256267,"version":"3.54.5"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T00:00:00Z","timestamp":1621468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Spinal cord injury (SCI) above the sacral level causes bladder dysfunction and remodeling with fibrosis. This study examined the antifibrotic effects using nintedanib, an inhibitor of vascular endothelial growth factor, fibroblast growth factor, and platelet\u2010derived growth factor receptors, on detrusor overactivity (DO) and bladder fibrosis, as well as the modulation mechanisms of C\u2010fiber afferent pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty female C57BL\/6 mice were divided into group A (spinal intact), group B (SCI with vehicle), and group C (SCI with nintedanib). At 2 weeks after SCI, vehicle or 50\u2009mg\/kg nintedanib was administered subcutaneously for 2 weeks. Then, cystometry was conducted, followed by RT\u2010PCR measurements of fibrosis\u2010related molecules, muscarinic, \u03b2\u2010adrenergic, TRP and purinergic receptors in the bladder or L6\u2010S1 dorsal root ganglia (DRG). Trichrome stain and Western blot analysis of transforming growth factor\u2010beta and fibronectin were performed in the bladder. TRPV1 expression in L6 DRG was measured by immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In cystometry, intercontraction intervals, nonvoiding contractions, voided volume, and voiding efficiency were significantly improved in group C versus group B. RT\u2010PCR, Western blotting, and trichrome staining revealed the fibrotic changes in the bladder of group B, which was improved in group C. Increased messenger RNA levels of TRPV1, TRPA1, P2X<jats:sub>2<\/jats:sub>, and P2X<jats:sub>3<\/jats:sub> in DRG of group B were significantly decreased in group C. TRPV1 immunoreactivity in DRG was increased in group B, but decreased in group C.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Nintedanib improves storage and voiding dysfunctions and bladder fibrosis in SCI mice. Also, nintedanib\u2010induced improvement of DO is associated with reduced expression of C\u2010fiber afferent markers, suggesting the modulation of bladder C\u2010fiber afferent activity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.24704","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T20:19:46Z","timestamp":1621541986000},"page":"1460-1469","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Antifibrosis treatment by inhibition of VEGF, FGF, and PDGF receptors improves bladder wall remodeling and detrusor overactivity in association with modulation of C\u2010fiber afferent activity in mice with spinal cord injury"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3781-5855","authenticated-orcid":false,"given":"Joonbeom","family":"Kwon","sequence":"first","affiliation":[{"name":"Department of Urology Daegu Fatima Hospital  Daegu South 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