Jie Min1, Bingshu Li1, Cheng Liu1, Shasha Hong1, Jianming Tang1, Ming Hu1, Yaodan Liu1, Suting Li1, Li Hong2. 1. Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. 2. Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. Electronic address: drhongli77@gmail.com.
Abstract
OBJECTIVE: To investigate the therapeutic effect and underlying molecular mechanism of electrical stimulation (ES) in a murine stress urinary incontinence (SUI) model. MATERIALS AND METHODS: Sixty female C57BL/6 mice were divided into 4 groups: CON group, no intervention; VD group, vaginal distension (VD) with an 8-mm dilator for 1 hour; VD + ES 20 group, 20 Hz ES for 0.5 hour for 7 days after VD; and VD + ES 50 group, 50 Hz ES for 7 days after VD. For functional studies, assessments of urodynamics and sneezing test were performed; then, anterior vaginal wall specimens were collected. Pathological changes were validated by Masson's trichrome and Van Gieson staining, and the expressions of collagen, transforming growth factor (TGF)-β1-Smad2/3 pathway components, and T-type calcium channels were detected by Western blotting and reverse transcription polymerase chain reaction. RESULTS: ES significantly increased maximum bladder capacity, leak point pressure, and sneezing positive rate in SUI mice. The staining results showed that collagen was disorganized in the VD group but became organized after ES, especially at 50 Hz. The same results were found for collagens I and III. The expression of TGF-β1, p-Smad2 and p-Smad3 significantly decreased in the VD group and significantly increased in the VD + ES groups, especially in the VD + ES 50 group. The expression of 2 T-type calcium channel subtypes (Cav 3.1 and Cav 3.2) decreased in the VD group compared with the CON group, but increased in the VD + ES group compared with the VD group. CONCLUSION: Dysregulation of collagen metabolism is involved in the pathogenesis of SUI. ES can ameliorate the symptoms of SUI by activating collagen regeneration through the TGFβ1-Smad2/3 pathway. T-type calcium channels might be involved in these processes.
OBJECTIVE: To investigate the therapeutic effect and underlying molecular mechanism of electrical stimulation (ES) in a murinestress urinary incontinence (SUI) model. MATERIALS AND METHODS: Sixty female C57BL/6 mice were divided into 4 groups: CON group, no intervention; VD group, vaginal distension (VD) with an 8-mm dilator for 1 hour; VD + ES 20 group, 20 Hz ES for 0.5 hour for 7 days after VD; and VD + ES 50 group, 50 Hz ES for 7 days after VD. For functional studies, assessments of urodynamics and sneezing test were performed; then, anterior vaginal wall specimens were collected. Pathological changes were validated by Masson's trichrome and Van Gieson staining, and the expressions of collagen, transforming growth factor (TGF)-β1-Smad2/3 pathway components, and T-type calcium channels were detected by Western blotting and reverse transcription polymerase chain reaction. RESULTS: ES significantly increased maximum bladder capacity, leak point pressure, and sneezing positive rate in SUI mice. The staining results showed that collagen was disorganized in the VD group but became organized after ES, especially at 50 Hz. The same results were found for collagens I and III. The expression of TGF-β1, p-Smad2 and p-Smad3 significantly decreased in the VD group and significantly increased in the VD + ES groups, especially in the VD + ES 50 group. The expression of 2 T-type calcium channel subtypes (Cav 3.1 and Cav 3.2) decreased in the VD group compared with the CON group, but increased in the VD + ES group compared with the VD group. CONCLUSION: Dysregulation of collagen metabolism is involved in the pathogenesis of SUI. ES can ameliorate the symptoms of SUI by activating collagen regeneration through the TGFβ1-Smad2/3 pathway. T-type calcium channels might be involved in these processes.
Authors: Wilke M Post; Joanna Widomska; Hilde Grens; Marieke J H Coenen; Frank M J Martens; Dick A W Janssen; Joanna IntHout; Geert Poelmans; Egbert Oosterwijk; Kirsten B Kluivers Journal: Int J Mol Sci Date: 2022-03-21 Impact factor: 5.923