The role of the ERK1/2 signalling pathway in the pathogenesis of female stress urinary incontinence

Huang, Qiong; Jin, Hong-Ying; Xie, Zhenwei; Wang, Min; Chen, Jian; Zhou, Yong

doi:10.1177/0300060513493995

Cited by 7 publications

(8 citation statements)

References 32 publications

(48 reference statements)

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“…AQPs are widely expressed in human tissue, including the skin (7), lung (8), vascular (9), and overexpression of AQPs has been reported in several types of human cancer (10)(11)(12). The roles of AQPs in pelvic support tissues and the pathology of female SUI remain unknown; however, the present study used anterior vaginal wall tissue as this is an important part of the periurethral support structure and has been previously examined (15,16). In the present study, immunohistochemical and immunofluorescence analysis revealed that AQP2 is expressed in the vaginal wall, including the fibroblasts, and that AQP2 protein expression in the anterior vaginal wall is decreased in patients with SUI.…”

Section: Discussionmentioning

confidence: 99%

“…After 3-5 days of primary culture, fibroblasts were digested with pancreatin for 2 min and passaged in culture bottles. The third generation of the cells were identified to be fibroblasts by morphological and immunohistochemical analysis, according to previous methods (15). The fibroblasts in the 3rd-6th generation were taken for experiments for identifying AQP2 by immunofluorescence.…”

Section: Methodsmentioning

confidence: 99%

“…3C) or α-smooth muscle actin (Fig. 3D) as described previously (15). In addition, immunofluorescence was performed to identify the location and expression of AQP2 in fibroblasts, as shown in Fig.…”

Section: Identification Of Aqp2 Expression In Fibroblasts By Immunoflmentioning

confidence: 99%

“…The authors previously demonstrated that AQP2 expression in the human endometrium varies during the menstrual cycle (14). The present study used anterior vaginal wall tissue as this is an important part of the periurethral support structure (15,16). The vaginal wall consists of a dense ECM, rich in collagen, that is maintained and remodeled by fibroblastic cells.…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Xie

et al. 2017

Molecular Medicine Reports

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Identification Of Aqp2 Expression In Fibroblasts By Immunoflmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Zhang

Xie

et al. 2017

Molecular Medicine Reports

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“…As in our previous studies, 12,13 biopsy samples of the anterior vaginal wall, used as urethral supporting tissue in SUI, were taken 1–2 cm from the uterine cervix, including mucosa, submucosa, connective tissue, and smooth muscle. All tissue was frozen immediately at −80°C for further analysis.…”

Section: Methodsmentioning

confidence: 99%

Endoplasmic reticulum stress contributes to the pathogenesis of stress urinary incontinence in postmenopausal women

Zhou

Liu

et al. 2018

J Int Med Res

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ObjectiveTo investigate the relationship between endoplasmic reticulum stress (ERS) and the pathogenesis of stress urinary incontinence (SUI) in postmenopausal women.MethodsAnterior vaginal wall tissue was collected from postmenopausal women with SUI and control subjects. Western blotting was performed for glucose-regulated protein (GRP78), inositol-requiring enzyme 1(IRE1), protein kinase-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), C/EBP-homologous protein (CHOP), and B-cell lymphoma 2 (Bcl-2). Additionally, mRNA expression levels of PERK, activating transcription factor 4 (ATF4), and CHOP were examined by real-time polymerase chain reaction.ResultsGRP78 protein and mRNA expression levels were significantly lower in women with SUI, compared with control subjects. PERK and p-PERK expression levels were higher in women with SUI than in control subjects. However, no differences in IRE1 or ATF6 expression levels were observed in either group. Notably, higher CHOP and lower Bcl-2 protein expression levels were detected in women with SUI, compared with control subjects. Furthermore, PERK, ATF4, and CHOP mRNA expression levels were significantly higher in women with SUI than in control subjects.ConclusionsAlterations of ERS markers in SUI suggest that ERS may be involved in the development of SUI in postmenopausal women.

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Mechanism of miR-34a in the metabolism of extracellular matrix in fibroblasts of stress urinary incontinence via Nampt-mediated autophagy

Zhou

Wang

2022

Cell Stress and Chaperones

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The role of the ERK1/2 signalling pathway in the pathogenesis of female stress urinary incontinence

Cited by 7 publications

References 32 publications

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

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

Endoplasmic reticulum stress contributes to the pathogenesis of stress urinary incontinence in postmenopausal women

Mechanism of miR-34a in the metabolism of extracellular matrix in fibroblasts of stress urinary incontinence via Nampt-mediated autophagy

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