Downregulation of AQP2 in the anterior vaginal wall is associated with the pathogenesis of female stress urinary incontinence

作者：Zhang, Zujuan; Xu, Pan; Xie, Zhenwei^*; Shen, Fengxian; Chen, Ning; Yu, Liming; He, Ronghuan

来源：Molecular Medicine Reports, 2017, 16(3): 3503-3509.

DOI：10.3892/mmr.2017.7014

• aquaporin-2
• stress urinary incontinence
• fibroblasts
• anterior vaginal wall
• collagen

The pathogenesis of stress urinary incontinence (SUI) is unclear. Aquaporins (AQPs) are a family of transmembrane proteins that transport water and small solutes, including glycerol, across cell membranes. AQPs have been demonstrated to serve a role in skin hydration, cellular proliferation, migration, immunity, wound healing and vascular remodeling in multiple organs. Furthermore, studies have confirmed that abnormal synthesis and degradation of collagens in extracellular matrix (ECM) remodeling contributes to SUI, by altering normal tissue architecture and mechanical properties. The authors previously demonstrated that AQP2 expressed in the human endometrium varies during the menstrual cycle. However, it is unknown whether AQP2 serves a role in the pathogenesis of SUI in the urethral supporting tissue. In the present study, AQP2 location and expression was examined in the anterior vaginal wall, and investigated the association between AQP2 and collagen I/III in female SUI. Western blotting, immunohistochemistry and immunofluorescence were used to measure AQP2 expression levels, and to reveal the location of AQP2 in the anterior vaginal wall, as well as fibroblasts in SUI and non-SUI. The association between AQP2 and collagen I/III was subsequently investigated by AQP2-small interfering RNA knockdown and overexpression 2 in fibroblasts. AQP2 expression in the anterior vaginal wall was significantly increased in women without SUI compared with those with SUI (P<0.05). Downregulation of AQP2 significantly decreased the mRNA and protein expression of collagen I/III, while AQP2 overexpression significantly increased the mRNA and protein expression of collagen I/III in fibroblasts (P<0.05). AQP2 was demonstrated to be expressed in the anterior vaginal wall and fibroblasts, and to regulate the expression level of collagen I/III in the anterior vaginal wall and fibroblasts, suggesting that AQP2 is associated with the pathogenesis of female SUI through collagen metabolism during ECM remodeling.

• 出版日期2017-9
• 单位浙江大学