Investigation of molecular factors associated with neurogenic bladder dysfunction by proteomic study
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Dept. of Medical Science/박사
Neurogenic bladder is dysfunction of the urinary bladder caused by the central nervous system or peripheral nerves. The primary causes of neurogenic bladder in children are congenital neural tube defects including myelomeningocele, lipomeningocele, and sacral agenesis. Histopathological changes are vaguely elucidated. To reveal molecular factors associated with neurogenic bladder dysfunction, we investigated differences between neurogenic and healthy bladders. The data of 7 patients with neurogenic bladder (M:F=4:3), a mean age of 9 years 3 months was compared to 6 patients with vesicoureteral reflux (VUR) serving as controls (M:F=4:2), a mean age of 10 months. Protein expressions were analyzed by 2D gel electrophoresis and Nanoflow LC-ESI-MS-MS analysis. Bladder smooth muscle cells (BSMCs) were cultured to investigate protein function and treated with siRNAs of TPI and Apo A-1 at various doses. After transfection, cell apoptosis was measured by flow cytometry.Among 16 protein spots were relatively overexpressed, and 20 spots were underexpressed in neurogenic bladders compared to controls. Triosephosphate isomerase (TPI) and apolipoprotein A-1 (Apo A-1), which are associated with apoptosis, were selected. The expressions of TPI and Apo A-1 were decreased in neurogenic bladder, and confirmed to be valid after western blot and masson’s trichrome staining. After TPI and Apo A-1 gene inhibition by siRNA, TPI and Apo A-1 expressions were dose-dependently decreased, and apoptotic cells were increased in BSMCs.Decreased TPI and Apo A-1 induce the apoptosis of myocytes in neurogenic bladder. The apoptosis of myocytes may cause bladder dysfunction. Therefore, these proteins would be potential targets for the treatment of or protection against the apoptosis of smooth muscle cells in neurogenic bladder.