LOX family enzymes expression in vaginal tissue of premenopausal women with severe pelvic organ prolapse

Alarab, May; Bortolini, Maria Augusta Tezelli; Drutz, Harold P.; Lye, Stephen J.; Shynlova, Oksana

doi:10.1007/s00192-010-1199-9

Cited by 42 publications

(48 citation statements)

References 26 publications

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“…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: 81%

“…In our previous studies enrolling a population controlled by hormonal status and ethnicity, we detected a significant reduction of LOX, LOX like 1 (LOXL1) and LOXL3 gene and protein levels in vaginal samples of Caucasian premenopausal patients with POP as compared to asymptomatic premenopausal women (15). 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).…”

Section: Introductionmentioning

confidence: 82%

“…We have previously described that the expression of LOX, LOXL1 and LOXL3 genes and proteins is diminished in premenopausal POP patients compared to asymptomatic controls (15). Here, we analyzed LOXs family genes and their possible association with POP in postmenopausal women.…”

Section: Postmenopausal Controls Postmenopausal Pop Patientsmentioning

confidence: 97%

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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: 81%

Section: Introductionmentioning

confidence: 82%

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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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“…LOXL1-deficient mice display POP, thinner vaginal wall, and lower urinary tract dysfunction through an inability of urogenital tissues to replenish elastic fibers after parturition (Liu et al, 2006). LOX and LOXL3 protein levels are significantly decreased in POP patients (Alarab et al, 2010;Zhao and Zhou, 2012). LOXL2 mRNA levels are significantly decreased in postmenopausal POP patients compared with asymptomatic postmenopausal controls (Drewes et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Estradiol plays a role in regulating the expression of lysyl oxidase family genes in mouse urogenital tissues and human Ishikawa cells

Zong

Jiang

Zhao

et al. 2015

J. Zhejiang Univ. Sci. B

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Abstract:The lysyl oxidase (LOX) family encodes the copper-dependent amine oxidases that play a key role in determining the tensile strength and structural integrity of connective tissues by catalyzing the crosslinking of elastin or collagen. Estrogen may upregulate the expression of LOX and lysyl oxidase-like 1 (LOXL1) in the vagina. The objective of this study was to determine the effect of estrogen on the expression of all LOX family genes in the urogenital tissues of accelerated ovarian aging mice and human Ishikawa cells. Mice and Ishikawa cells treated with estradiol (E2) showed increased expression of LOX family genes and transforming growth factor β1 (TGF-β1). Ishikawa cells treated with TGF-β1 also showed increased expression of LOX family genes. The Ishikawa cells were then treated with either E2 plus the TGF-β receptor (TGFBR) inhibitor SB431542 or E2 alone. The expression of LOX family genes induced by E2 was reduced in the Ishikawa cells treated with TGFBR inhibitor. Our results showed that E2 increased the expression of the LOX family genes, and suggest that this induction may be mediated by the TGF-β signal pathway. E2 may play a role in regulating the expression of LOX family genes.

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“…Alarab и соавт. [21] выяснили, что у пациенток с ПГ в фибробластах и клетках мышечной ткани значи-тельно снижена экспрессия генов лизилоксидазы (LOX) и лизилоксидазоподобных ферментов L1 и L3 (LOXL1, LOXL3). Данные ферменты катализируют процессы посттрансляционных модификаций колла-гена и эластина и образования стабильных кросс-сшивок между ними, что играет важную роль в поддер-жании целостности ЭЦМ.…”

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Modern molecular genetic and biochemical predictors of genital prolapse (a review)

Lukyanova¹,

Smolnova²,

Adamyan³

2016

Probl. reprod.

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analysis of published data on genetic polymorphisms and biochemical mechanisms of genital prolapse is presented. The paper prasents the modern data on the impact of genetic polymorphisms on genital prolapse predisposition. It describes appropriate molecular genetic and biochemical processes of pathological connective tissue formation of pelvic organs and the pelvic complex in women with genital prolapse, including the background of connective tissue dysplasia syndromе.

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LOX family enzymes expression in vaginal tissue of premenopausal women with severe pelvic organ prolapse

Abstract: We proposed that reduced expression of LOX enzymes may result in defective assembly of pelvic tissues and development of POP.

Cited by 42 publications

References 26 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

Estradiol plays a role in regulating the expression of lysyl oxidase family genes in mouse urogenital tissues and human Ishikawa cells

Modern molecular genetic and biochemical predictors of genital prolapse (a review)

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