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- Title
Upregulation of neurotrophins and transforming growth factor‐β expression in the bladder may lead to nerve hyperplasia and fibrosis in patients with severe ketamine‐associated cystitis.
- Authors
Jhang, Jia‐Fong; Wang, Hsiu‐Jen; Hsu, Yung‐Hsiang; Birder, Lori A.; Kuo, Hann‐Chorng
- Abstract
Aims: To investigate the mechanism of bladder nerve hyperplasia and fibrosis in the patients with ketamine‐associated cystitis (KC). Methods: 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‐100 to evaluated nerve hyperplasia. The quantitative Western blot analysis was performed for NGF, brain‐derived neurotrophic factor (BDNF), growth‐associated protein 43 (GAP‐43), tropomyosin receptor kinase A and B (TrkA and TrkB), transforming growth factor‐β (TGF‐β), phosphorylated extracellular signal‐regulated kinases (p‐ERK), protein kinase B (p‐Akt), and glycogen synthase kinase 3β (p‐GSK‐3β). Results: The results demonstrated diffuse NGF expression in KC bladder epithelium, lamina propria, and muscle. The GAP‐43, NGF, BDNF, TrkA, TGF‐β, p‐ERK, P‐AKT, and p‐GSK‐3β 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‐100 staining. TGF‐β expression in the bladder specimens was significantly correlated with neurotrophins, p‐ERK, P‐AKT, and p‐GSK‐3β levels. Conclusion: Our findings indicate upregulation of neurotrophins, TGF‐β, 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‐β interact as cause and effect, leading to bladder hypersensitivity and fibrosis in severe KC.
- Subjects
NEUROTROPHINS; GAP Inc.; BRAIN-derived neurotrophic factor; NERVE growth factor; EXTRACELLULAR signal-regulated kinases; GLYCOGEN synthase kinase; PROTEIN kinase B
- Publication
Neurourology & Urodynamics, 2019, Vol 38, Issue 8, p2303
- ISSN
0733-2467
- Publication type
Article
- DOI
10.1002/nau.24139