Expression of Extracellular Matrix-Remodeling Proteins Is Altered in Vaginal Tissue of Premenopausal Women With Severe Pelvic Organ Prolapse

Alarab, May; Kufaishi, Hala; Lye, Stephen J.; Drutz, Harold P.; Shynlova, Oksana

doi:10.1177/1933719113512529

Cited by 54 publications

(59 citation statements)

References 32 publications

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“…In addition, the expression and the activity of MMPs were increased whereas the expression of all TIMPs was significantly decreased in samples of vaginal tissue taken from premenopausal women with POP compared to controls (16). It is plausible that deficient or defective ECM metabolism enzymes represent key factors responsible for the development of POP.…”

Section: Introductionmentioning

confidence: 93%

“…Based on our previous findings indicating that vaginal tissues from Caucasian premenopausal POP women show altered ECM metabolism (15,16), and that menopause-related ovarian hormones deprivation influences the genesis of POP in women (17), we also believe that similar or different changes can be found in POP women after the menopause. Therefore, the three objectives of the present study were to identify the expression pattern of MMPs, TIMPs and LOXs family genes (Table-1) in the anterior vaginal tissue of Caucasian (1) premenopausal women without POP according to the menstrual cycle phase (proliferative vs secretory) , (2) to investigate the effect of age--related menopause changes on their expression by comparing premenopausal vs. postmenopausal women without POP.…”

Section: Introductionmentioning

confidence: 99%

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Genes responsible for vaginal extracellular matrix metabolism are modulated by women's reproductive cycle and menopause

Shynlova

Bortolini²,

Alarab

2013

Int. braz j urol.

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Objectives: To analyze the expression of genes involved in extracellular matrix (ECM) biogenesis and remodeling in vaginal tissue of women with clinically normal pelvic floor support (defined as controls) according to the phase of menstrual cycle and postmenopausal women with and without pelvic organ prolapse (POP). Materials and Methods:This study examined the expression of matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and the Lysyl oxidase (LOX) family genes in the anterior vaginal wall of Caucasian women by real-time RT-PCR. Initially, mRNA expression was assessed in premenopausal controls in the secretory (group 1, n = 10) vs. proliferative (group 2, n = 8) phase of menstrual cycle. In addition, we compared premenopausal controls in the proliferative phase (group 2) vs. postmenopausal controls (group 3, n = 5). Finally, we analyzed postmenopausal controls (group 3) vs. postmenopausal women with advanced POP (group 4, n = 13). Results: According to the phase of menstrual cycle, MMP1 was significantly reduced (p = 0.003), whereas the expression of TIMP1 and LOXL4 was significantly up-regulated during proliferative phase (both p < 0.01) when compared to the secretory phase in premenopausal control women. Regarding menopausal status/ageing, all MMPs were down--regulated, while TIMP3, TIMP4 and LOXL2 were significantly up-regulated in postmenopausal control women when compared to premenopausal controls (p = 0.005, p = 0.01 and p < 0.001, correspondingly). TIMP4 and LOXL2 mRNA levels were significantly decreased in postmenopausal POP patients compared to asymptomatic postmenopausal controls (p < 0.01 for both). Conclusions: Our results indicate that ovarian cycle and age-related changes influence the expression of genes encoding proteins responsible for ECM metabolism in human vagina. Moreover, POP is associated with alteration in vaginal ECM components after menopause.

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Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Genes responsible for vaginal extracellular matrix metabolism are modulated by women's reproductive cycle and menopause

Shynlova

Bortolini²,

Alarab

2013

Int. braz j urol.

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“…While collagen type I and III have been shown to increase with prolapse, others have suggested that the ratio of collagen type III to type I decreases21. Irrespective, it appears that the collagen remodels with the onset of prolapse, due to increased expression of matrix metalloproteinases (MMP)-2 and -1222. This is further exacerbated during the progression of prolapse by an increase in other matrix metalloproteinases, active MMP-9 and a decrease in fibulin 5, essential for elastogenesis23.…”

mentioning

confidence: 99%

“…This is further exacerbated during the progression of prolapse by an increase in other matrix metalloproteinases, active MMP-9 and a decrease in fibulin 5, essential for elastogenesis23. There is also a decrease in the transcriptional regulator, Homeobox protein Hox-A13 ( HOXA13 ), which controls the expression of ECM associated genes involved in elastic fibre homeostasis24 in vaginal tissue22. Elastic fibres play an important role in the mechanical properties of the vaginal wall, allowing the tissue to extend and return to its original shape without damage25 particularly during pregnancy26.…”

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confidence: 99%

Ovine multiparity is associated with diminished vaginal muscularis, increased elastic fibres and vaginal wall weakness: implication for pelvic organ prolapse

Emmerson

Young

Rosamilia

et al. 2017

Sci Rep

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Pelvic Organ Prolapse (POP) is a major clinical burden affecting 25% of women, with vaginal delivery a major contributing factor. We hypothesised that increasing parity weakens the vagina by altering the extracellular matrix proteins and smooth muscle thereby leading to POP vulnerability. We used a modified POP-quantification (POP-Q) system and a novel pressure sensor to measure vaginal wall weakness in nulliparous, primiparous and multiparous ewes. These measurements were correlated with histological, biochemical and biomechanical properties of the ovine vagina. Primiparous and multiparous ewes had greater displacement of vaginal tissue compared to nulliparous at points Aa, Ap and Ba and lower pressure sensor measurements at points equivalent to Ap and Ba. Vaginal wall muscularis of multiparous ewes was thinner than nulliparous and had greater elastic fibre content. Collagen content was lower in primiparous than nulliparous ewes, but collagen organisation did not differ. Biomechanically, multiparous vaginal tissue was weaker and less stiff than nulliparous. Parity had a significant impact on the structure and function of the ovine vaginal wall, as the multiparous vaginal wall was weaker and had a thinner muscularis than nulliparous ewes. This correlated with “POP-Q” and pressure sensor measurements showing greater tissue laxity in multiparous compared to nulliparous ewes.

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“…Over the last few years, a number of researchers have focused on the association between solid tumor ECM remodeling and malignant behavior (21,22). Previously published results have indicated that the remodeling of the ECM is important in the progression of Pca (23–25).…”

Section: Discussionmentioning

confidence: 99%

Low extracellular lysyl oxidase expression is associated with poor prognosis in patients with prostate cancer

et al. 2016

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Remodeling of the extracellular matrix (ECM), which is induced by lysyl oxidase (LOX), has been demonstrated to accompany tumor progression; however, the association between LOX expression levels and the malignant behavior of prostate cancer (Pca) remains unclear. The present study aimed to analyze the tumor-associated expression profile of LOX in patients with Pca and to evaluate its potential prognostic value. In the form of a retrospective study, the expression patterns of LOX and collagen I were analyzed in patients with benign prostate hyperplasia and Pca by immunohistochemical examination. The results demonstrated that, with the initiation and progression of Pca, the expression levels of LOX and collagen I were closely associated with Gleason score and tumor stage. In addition, although LOX was expressed in cancer and non-cancer tissues, the differential expression pattern observed in the ECM of Pca cells may indicate that LOX is an important molecule that affects the progression of this disease. Therefore, LOX expression level in the ECM may function as an independent predictor of Pca.

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Expression of Extracellular Matrix-Remodeling Proteins Is Altered in Vaginal Tissue of Premenopausal Women With Severe Pelvic Organ Prolapse

Abstract: Expression of ECM-remodeling proteins is altered in the vagina of premenopausal patients with severe POP. We speculate that dysregulation of MMP/TIMP complexes and ADAMTS-2 proteins may cause connective tissue defects, which result in weakened vaginal wall support and POP development.

Cited by 54 publications

References 32 publications

Genes responsible for vaginal extracellular matrix metabolism are modulated by women's reproductive cycle and menopause

Genes responsible for vaginal extracellular matrix metabolism are modulated by women's reproductive cycle and menopause

Ovine multiparity is associated with diminished vaginal muscularis, increased elastic fibres and vaginal wall weakness: implication for pelvic organ prolapse

Low extracellular lysyl oxidase expression is associated with poor prognosis in patients with prostate cancer

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