{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T05:52:09Z","timestamp":1791870729315,"version":"4.3.4"},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T00:00:00Z","timestamp":1566345600000},"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":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To investigate the mechanism of bladder nerve hyperplasia and fibrosis in the patients with ketamine\u2010associated cystitis (KC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sixteen patients with severe KC, six patients with mild KC, and five patients with localized invasive bladder cancer served as control patients. Bladder mucosa specimens were taken during the operations, and the specimens were stained for nerve growth factor (NGF) and S\u2010100 to evaluated nerve hyperplasia. The quantitative Western blot analysis was performed for NGF, brain\u2010derived neurotrophic factor (BDNF), growth\u2010associated protein 43 (GAP\u201043), tropomyosin receptor kinase A and B (TrkA and TrkB), transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2), phosphorylated extracellular signal\u2010regulated kinases (p\u2010ERK), protein kinase B (p\u2010Akt), and glycogen synthase kinase 3\u03b2 (p\u2010GSK\u20103\u03b2).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The results demonstrated diffuse NGF expression in KC bladder epithelium, lamina propria, and muscle. The GAP\u201043, NGF, BDNF, TrkA, TGF\u2010\u03b2, p\u2010ERK, P\u2010AKT, and p\u2010GSK\u20103\u03b2 expression in the bladder mucosa specimens of patients with severe KC was significantly higher than in patients with mild KC and control patients. Expression of neurotrophins was significantly correlated with bladder capacity and pain. NGF and BDNF expression were significantly higher in the KC bladder specimens with strongly positive S\u2010100 staining. TGF\u2010\u03b2 expression in the bladder specimens was significantly correlated with neurotrophins, p\u2010ERK, P\u2010AKT, and p\u2010GSK\u20103\u03b2 levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings indicate upregulation of neurotrophins, TGF\u2010\u03b2, and activation of the cell proliferation kinases plays an important role in nerve hyperplasia and fibrosis mechanisms in severe KC bladders. The neurotrophins and TGF\u2010\u03b2 interact as cause and effect, leading to bladder hypersensitivity and fibrosis in severe KC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/nau.24139","type":"journal-article","created":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T07:19:46Z","timestamp":1566371986000},"page":"2303-2310","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Upregulation of neurotrophins and transforming growth factor\u2010\u03b2 expression in the bladder may lead to nerve hyperplasia and fibrosis in patients with severe ketamine\u2010associated cystitis"],"prefix":"10.1002","volume":"38","author":[{"given":"Jia\u2010Fong","family":"Jhang","sequence":"first","affiliation":[{"name":"Department of Urology, Hualien Tzu Chi General Hospital Buddhist Tzu Chi Medical Foundation, and Tzu Chi University  Hualien 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