Microarray analysis of differentially expressed genes in vaginal tissues from women with stress urinary incontinence compared with asymptomatic women

Chen, Bertha; Wen, Yan; Zhang, Zhaomei; Guo, Yaqian; Warrington, Janet A.; Polan, Mary Lake

doi:10.1093/humrep/dei276

Cited by 46 publications

(38 citation statements)

References 28 publications

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“…Numerous genes, including actin, myosin, ECM-associated genes and transcription factors, have been studied and shown to be associated with POP (11–13). However, there have been a limited number of studies investigating the role of immune-associated genes in POP.…”

Section: Discussionmentioning

confidence: 99%

Interferon-γ and its pathway-associated gene expression in the vaginal tissue of premenopausal females with pelvic organ prolapse

Zhao¹,

Jiang²,

Wu³

et al. 2014

Experimental and Therapeutic Medicine

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Interferon (IFN)-γ is a potent proinflammatory molecule. However, few studies have investigated the expression levels of IFN-γ during pelvic organ prolapse (POP). In the present study, the expression levels and tissue localization of IFN-γ and its pathway-associated genes were detected in the vaginal walls of premenopausal females with POP and asymptomatic controls using quantitative polymerase chain reaction and immunohistochemistry. When compared with the matched controls, an 8.6-fold increase in IFN-γ, 3.8-fold increase in IFN-γ receptor (IFNGR)1, 2.6-fold increase in IFNGR2, 3.4-fold increase in signal transducer and activator of transcription-1, 2.2-fold increase in janus kinase-1 and 5.1-fold increase in nuclear factor (NF)-κB mRNA expression levels were observed in the females with premenopausal POP. In all the females with POP, higher mRNA expression levels of IFN-γ and its receptors were observed when compared with the controls. Expression levels of all the proteins were detected by immunohistochemistry, and the results demonstrated higher staining for IFN-γ, IFNGRs and pathway-associated genes in females with POP. Therefore, the results indicated that IFN-γ may be used as an inflammatory marker for POP development, and is associated with NF-κB.

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Section: Discussionmentioning

confidence: 99%

Interferon-γ and its pathway-associated gene expression in the vaginal tissue of premenopausal females with pelvic organ prolapse

Zhao¹,

Jiang²,

Wu³

et al. 2014

Experimental and Therapeutic Medicine

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“…Few data have shown that overall collagen metabolism is activated in the proliferative phase, while elastin metabolism changes are more pronounced in the secretory phase of the menstrual cycle (23,24). It is well described that reproductive organs are influenced by ovarian hormones during the menstrual cycle, pregnancy and menopause.…”

Section: Discussionmentioning

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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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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“…Nevertheless, other investigators have shown an increase or no changes in collagen expression in patients with SUI and other FPFD (Falconer et al 1998). Changes, both increases and decreases, of various other ECM components have also been reported (Chen et al 2006). The challenge is determining whether those changes are the cause of the condition, or the eVect of other, as of yet unidentiWed causes.…”

Section: Introductionmentioning

confidence: 94%

Sequence variant in the laminin γ1 (LAMC1) gene associated with familial pelvic organ prolapse

et al. 2006

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Pelvic organ prolapse is a common condition, affecting up to a third of women throughout their lifetime. Genetic factors are believed to account for about 30% of the incidence, and are the least understood component of the disorder. Familial cases, particularly those in which prolapse manifests in young women, are especially valuable in the effort to find the genes involved. We recently reported autosomal dominant transmission as the most likely mode of inheritance, based on a collection of families with high incidence of prolapse. Of greatest interest was a family in which three generations of female relatives suffered from prolapse at a very young age. A genome-wide linkage scan performed using the Affymetrix GeneChip Human mapping 10K array identified ten regions with a LOD score of 1.5, the maximum possible for this family. Candidate genes within those regions were analyzed for expression in vaginal tissue by RT-PCR. Of the genes confirmed to be expressed, LAMC1 was further evaluated by sequencing and select single nucleotide polymorphism (SNP) genotyping for causative sequence variants in affected family members. We identified one such SNP, rs10911193. The rare T variant segregating with the condition is present at a frequency of 4.9% in the general population and 22% among probands from our cohort of families. It affects the binding site for NFIL3, a transcription factor that we verified to be co-expressed in vaginal tissue. Altogether these data suggest that a polymorphism in the promoter of LAMC1 may increase the susceptibility to early-onset pelvic organ prolapse.

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Microarray analysis of differentially expressed genes in vaginal tissues from women with stress urinary incontinence compared with asymptomatic women

Abstract: Genes involved in elastin metabolism were differentially expressed in vaginal tissue from women with SUI, suggesting that elastin remodelling may be important in the molecular aetiology of SUI.

Cited by 46 publications

References 28 publications

Interferon-γ and its pathway-associated gene expression in the vaginal tissue of premenopausal females with pelvic organ prolapse

Interferon-γ and its pathway-associated gene expression in the vaginal tissue of premenopausal females with pelvic organ prolapse

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

Sequence variant in the laminin γ1 (LAMC1) gene associated with familial pelvic organ prolapse

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