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

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

doi:10.3892/mmr.2017.7014

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

Authors:
- Zujuan Zhang
- Pan Xu
- Zhenwei Xie
- Fengxian Shen
- Ning Chen
- Liming Yu
- Ronghuan He
View Affiliations

Affiliations: Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China
Published online on: July 15, 2017 https://doi.org/10.3892/mmr.2017.7014
Pages: 3503-3509

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

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.

View Figures

View References

1	Zhu L, Lang J, Liu C, Han S, Huang J and Li X: The epidemiological study of women with urinary incontinence and risk factors for stress urinary incontinence in China. Menopause. 16:831–836. 2009. View Article : Google Scholar : PubMed/NCBI
2	Luginbuehl H, Baeyens JP, Kuhn A, Christen R, Oberli B, Eichelberger P and Radlinger L: Pelvic floor muscle reflex activity during coughing-an exploratory and reliability study. Ann Phys Rehabil Med. 59:302–307. 2016. View Article : Google Scholar : PubMed/NCBI
3	Chai TC, Richter HE, Moalli P, Keay S, Biggio J, Zong W, Curto T, Kim HY, Stoddard AM and Kusek JW: Inflammatory and tissue remodeling urinary biomarkers before and after mid urethral sling surgery for stress urinary incontinence. J Urol. 191:703–709. 2014. View Article : Google Scholar : PubMed/NCBI
4	Malone L, Schuler C, Leggett RE and Levin RM: Effect of estrogen and ovariectomy on response of the female rabbit urinary bladder to two forms of in vitro oxidative stress. Int Urogynecol J. 25:791–798. 2014. View Article : Google Scholar : PubMed/NCBI
5	Chan SSC, Cheung RYK, Lee LL, Choy RKW and Chung TKH: A longitudinal follow-up of levator ani muscle avulsion: Does a second delivery affect it? Ultrasound Obstet Gynecol. Jul 1–2016.(Epub ahead of print).
6	Sumino Y, Yoshikawa S, Mori K, Mimata H and Yoshimura N: IGF-1 as an important endogenous growth factor for recovery from impaired urethral continence function in rats with simulated childbirth injury. J Urol. 195:1927–1935. 2016. View Article : Google Scholar : PubMed/NCBI
7	Sebastian R, Chau E, Fillmore P, Matthews J, Price LA, Sidhaye V and Milner SM: Epidermal aquaporin-3 is increased in the cutaneous burn wound. Burns. 41:843–847. 2015. View Article : Google Scholar : PubMed/NCBI
8	Liang X, Zhang B, Chen Q, Zhang J, Lei B, Li B, Wei Y, Zhai R, Liang Z, He S and Tang B: The mechanism underlying alpinetin-mediated alleviationof pancreatitis-associated lung injury through upregulating aquaporin-1. Drug Des Devel Ther. 10:841–850. 2016.PubMed/NCBI
9	Iguchi H, Oda M, Yamazaki H and Yokomori H: Participation of aquaporin-1 in vascular changes and remodeling in cirrhotic liver. Med Mol Morphol. 46:123–132. 2013. View Article : Google Scholar : PubMed/NCBI
10	Chen J, Wang Z, Xu D, Liu Y and Gao Y: Aquaporin 3 promotes prostate cancer cell motility and invasion via extracellular signal-regulated kinase 1/2-mediated matrix metalloproteinase-3 secretion. Mol Med Rep. 11:2882–2888. 2015.PubMed/NCBI
11	Dorward HS, Du A, Bruhn MA, Wrin J, Pei JV, Evdokiou A, Price TJ, Yool AJ and Hardingham JE: Pharmacological blockade of aquaporin-1 water channel by AqB013 restricts migration and invasiveness of colon cancer cells and prevents endothelial tube formation in vitro. J Exp Clin Cancer Res. 35:362016. View Article : Google Scholar : PubMed/NCBI
12	Cao XC, Zhang WR, Cao WF, Liu BW, Zhang F, Zhao HM, Meng R, Zhang L, Niu RF, Hao XS, et al: Aquaporin3 is required for FGF-2-induced migration of human breast cancers. PLoS One. 8:e567352013. View Article : Google Scholar : PubMed/NCBI
13	Chen B and Yeh J: Alterations in connective tissue metabolism in stress incontinence and prolapse. J Urol. 186:1768–1772. 2011. View Article : Google Scholar : PubMed/NCBI
14	He RH, Sheng JZ, Luo Q, Jin F, Wang B, Qian YL, Zhou CY, Sheng X and Huang HF: Aquaporin-2 expression in human endometrium correlates with serum ovarian steroid hormones. Life Sci. 79:423–429. 2006. View Article : Google Scholar : PubMed/NCBI
15	Huang Q, Jin H, Xie Z, Wang M, Chen J and Zhou Y: The role of the ERK1/2 signalling pathway in the pathogenesis of female stress urinary incontinence. J Int Med Res. 41:1242–1251. 2013. View Article : Google Scholar : PubMed/NCBI
16	Wu Y, Zhang L, Jin H, Zhou J and Xie Z: The role of calpain-calpastatin system in the developmentof stress urinary incontinence. Int Urogynecol J. 21:63–68. 2010. View Article : Google Scholar : PubMed/NCBI
17	Ruiz-Zapata AM, Kerkhof MH, Ghazanfari S, Zandieh-Doulabi B, Stoop R, Smit TH and Helder MN: Vaginal fibroblastic cells from women with pelvic organ prolapse produce matrices with increased stiffness and collagen content. Sci Rep. 6:229712016. View Article : Google Scholar : PubMed/NCBI
18	Haylen BT, de Ridder D, Freeman RM, Swift SE, Berghmans B, Lee J, Monga A, Petri E, Rizk DE, Sand PK and Schaer GN: An international urogynecological association (IUGA)/international continence society (ICS) joint report on the terminology for female pelvic floor dysfunction. Int Urogynecol J. 21:5–26. 2010. View Article : Google Scholar : PubMed/NCBI
19	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
20	Ruiz-Zapata AM, Kerkhof MH, Zandieh-Doulabi B, Brölmann HA, Smit TH and Helder MN: Functional characteristics of vaginal fibroblastic cells from premenopausal women with pelvic organ prolapse. Mol Hum Reprod. 20:1135–1143. 2014. View Article : Google Scholar : PubMed/NCBI
21	Han L, Wang L, Wang Q, Li H and Zang H: Association between pelvic organ prolapse and stress urinary incontinence with collagen. Exp Ther Med. 7:1337–1341. 2014.PubMed/NCBI
22	Mangera A, Bullock AJ, Roman S, Chapple CR and MacNeil S: Comparison of candidate scaffolds for tissue engineering for stress urinary incontinence and pelvic organ prolapse repair. BJU Int. 112:674–685. 2013. View Article : Google Scholar : PubMed/NCBI