Changes in the extracellular matrix in periurethral tissue of women with stress urinary incontinence

Goepel, Christian; Thomssen, Christoph

doi:10.1016/j.acthis.2006.07.001

Cited by 33 publications

(30 citation statements)

References 24 publications

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“…Interestingly, CDH2 engagement did not have the same effects, suggesting that CDH11 might be a distinct target for preventing fibrosis and promoting tissue regeneration. By contrast, a number of diseases are attributed to a loss or impaired state of the ECM, for example, stress urinary incontinence or improper bladder function, which is related to irregular distribution of elastin fibers (Goepel and Thomssen, 2006) and reduced collagen type I and III (Li et al, 2012a), and Marfan's syndrome, which is caused by a mutation in the fibrillin gene leading to lack of elastin fibers and reduced tissue levels of TGF-β in the aorta, with subsequent increase in stiffness (Benke et al, 2013). However, loss of CDH11 had no effect on the mRNA expression of the fibrillin gene, as shown in Cdh11 −/− mouse dermal fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

“…As a result, loss of collagen and/or elastin has been implicated in many diseases and is welldocumented in aging (Kohl et al, 2011;Wagenseil and Mecham, 2012). For example, fragmented or irregular distribution of collagen and elastin fibrils have been implicated in bladder incontinence as well as cardiovascular disorders such as hypertension, aneurysms and Marfan's syndrome (Goepel and Thomssen, 2006;Li, 2012a;Benke et al, 2013). By contrast, excessive and cumulative deposition of collagen disrupts organ architecture, leading to scar formation and loss of function.…”

Section: Introductionmentioning

confidence: 99%

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Cadherin-11 is a novel regulator of extracellular matrix synthesis and tissue mechanics

Row

Liu

Alimperti

et al. 2016

Journal of Cell Science

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We discovered that Cadherin-11 (CDH11) regulates collagen and elastin synthesis, both affecting the mechanical properties and contractile function of animal tissues. Using a Cdh11-null mouse model, we observed a significant reduction in the mechanical properties [Youngs' modulus and ultimate tensile strength (UTS)] of Cdh11 −/− as compared to wild-type (WT) mouse tissues, such as the aorta, bladder and skin. The deterioration of mechanical properties (Youngs' modulus and UTS) was accompanied by reduced collagen and elastin content in Cdh11 −/− mouse tissues as well as in cells in culture. Similarly, knocking down CDH11 abolished collagen and elastin synthesis in human cells, and consequently reduced their ability to generate force. Conversely, engagement of CDH11 through homophilic interactions, led to swift activation of the TGF-β and ROCK pathways as evidenced by phosphorylation of downstream effectors. Subsequently, activation of the key transcription factors, MRTF-A (also known as MKL1) and MYOCD led to significant upregulation of collagen and elastin genes. Taken together, our results demonstrate a novel role of adherens junctions in regulating extracellular matrix (ECM) synthesis with implications for many important biological processes, including maintenance of tissue integrity, wound healing and tissue regeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cadherin-11 is a novel regulator of extracellular matrix synthesis and tissue mechanics

Row

Liu

Alimperti

et al. 2016

Journal of Cell Science

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“…Abnormal elastin homeostasis was also noted in women with stress UI (Soderberg et al, 2009;Goepel and Thomssen, 2006;Wen et al, 2007;Chen et al, 2007). These findings support the role of connective tissue disturbances, especially elastins', in the evolution of POP and UI.…”

Section: Introductionmentioning

confidence: 74%

“…These findings clearly indicate the role of elastin in the maintenance of normal pelvic support and its absence or damage in POP. Abnormal elastin homeostasis has also been noted in women with stress UI (Soderberg et al, 2009;Goepel and Thomssen, 2006;Chen et al, 2007). Based on previous studies it is recognized that TGF-1 is a strong stimulator of elastin (Choi et al, 2009;Kahari et al, 1992).…”

Section: Commentmentioning

confidence: 99%

Levormeloxifene inhibits vaginal tropoelastin and transforming growth factor beta 1 production

Takács

Yavagal

Zhang

et al. 2011

J. Smooth Muscle Res.

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“…2 The functionality of ECM is maintained via the secretion of proteases and growth factors by connective tissue cells that modulate ECM remodelling (ECM metabolism). 3 Imbalances in ECM metabolism may therefore weaken the periurethral support structure, leading to a failure of pelvic support and increasing urethral hypermobility and involuntary urine leakage.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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Objective: To investigate the role of extracellular-regulated protein kinase (ERK)1/2 and phosphorylated (p)-ERK1/2 in the pathogenesis of female stress urinary incontinence (SUI). Methods: Anterior vaginal wall tissue was collected from women with SUI and control subjects. Immunohistochemistry and Western blotting were performed for p-ERK1/2. Primary vaginal fibroblast cultures were incubated in the presence or absence of PD98059 (an inhibitor of ERK kinase) and levels of collagen I and III mRNA and protein were examined by quantitative reverse transcription-polymerase chain reaction and Western blot, respectively. Results: Levels of p-ERK1/2 were significantly lower in vaginal wall tissue from patients with SUI (n ¼ 10) compared with controls (n ¼ 10). PD98059 treatment significantly reduced levels of collagen I and III mRNA and protein.Conclusions: Female SUI is associated with reduced levels of p-ERK1/2 compared with controls, and inhibition of the ERK1/2 signalling pathway inhibits collagen type I and III synthesis in vaginal wall fibroblasts.

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Changes in the extracellular matrix in periurethral tissue of women with stress urinary incontinence

Cited by 33 publications

References 24 publications

Cadherin-11 is a novel regulator of extracellular matrix synthesis and tissue mechanics

Cadherin-11 is a novel regulator of extracellular matrix synthesis and tissue mechanics

Levormeloxifene inhibits vaginal tropoelastin and transforming growth factor beta 1 production

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

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