Changes in transcription profile in pelvic organ fibroblasts in response to stretch
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE6862 | GEO | 2007/01/26
SECONDARY ACCESSION(S): PRJNA99109
REPOSITORIES: GEO
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Project description:Purpose: Damage to the uterosacral ligaments is an important contributor to uterine and vaginal prolapse. The aim of this study was to identify differentially expressed proteins in the uterosacral ligaments of women with and without pelvic organ prolapse and analyze their relationships to cellular mechanisms involved in the pathogenesis of pelvic organ prolapse. Experimental Design: Uterosacral ligament connective tissue from four patients with pelvic organ prolapse and four control women underwent iTRAQ analysis followed by Ingenuity Pathway Analysis of differentially expressed proteins. Differentially expressed proteins were valideated using western blot analysis. Results: A total of 1789 unique protein sequences were identified in the uterosacral ligament connective tissues. 88 proteins had expression levels that were significantly different between prolapse and control groups (≥1.2-fold). Ingenuity pathway analysis demonstrated 14 differentially expressed proteins that were associated with "Connective Tissue Function". Among them, fibromodulin(FMOD), Collagen alpha-1 (XIV) chain(COL14A1), Calponin-1 (CNN-1), Tenascin (TNC), and Galectin-1(LGALS1 appeared most likely to play a role in the etiology of pelvic organ prolapse. Conclusions and clinical relevence: We identified at least 6 proteins not previously associated with the pathogenesis of pelvic organ prolapse with biologic functions that suggest a plausible relationship to the disorder. These results may be helpful for furthering our understanding of the pathophysiological mechanisms of pelvic organ prolapse.
2018-12-10 | PXD011467 | Pride
Project description:Introduction and Hypothesis: Identify processes contributing to pelvic organ prolapse (POP) by transcriptional profiling of pelvic connective tissue in conjunction with light microscopy. Methods: We performed a frequency matched case-control study of women undergoing hysterectomy. Total RNA, extracted from uterosacral and round ligament samples used to generate labeled cRNA, was hybridized to microarrays and analyzed for the expression of 32,878 genes. Significance Analysis of Microarrays, (Stanford University, CA), identified differentially expressed genes used for ontoanalysis, and quantitative PCR (qPCR) confirmed results. Light microscopy confirmed tissue type and assessed inflammatory infiltration. Results: The analysis of thirty-four arrays revealed 249 differentially expressed genes with fold changes larger than 1.5 fold and false discovery rates M-bM-^IM-$5.2%. Immunity and Defense was the most significant biological process differentially expressed in POP. Selected qPCR confirmed 4 genes. Light microscopy showed no inflammatory infiltrates. Conclusions: Genes enriched for Immunity and Defense contribute to POP independent of inflammatory infiltrates. Keywords: whole tissue (endopelvic fascia) type comparison This was a group matched case control study of 8 women with pelvic organ prolapse versus 9 non-prolapse controls, both undergoing hysterectomy for benign conditions. Two separate pelvic support tissues were collected from each patient. The uterosacral ligament and round ligament tissue was removed at the time of hysterectomy, RNA was extracted and ABI whole genome chips used to identify differences in expression profiles of individual samples. Various ethnic groups, age groups and menopausal status were included.
2008-09-19 | E-GEOD-12852 | biostudies-arrayexpress
Project description:Pelvic organ prolapse (POP) affects a large proportion of adult women. With the increase in global population ageing, the prevalence of POP is expected to increase in upcoming decades, which will impose a substantial medical burden. Therefore, suitable therapeutical target is important. However, due to the pathogenesis of POP is still unclear, it leads to the failure of POP repair. Herein, we identified changes in ncRNA, and mRNAs in the anterior vaginal wall and uterosacral ligament in patients with POP, providing new insights into the pathogenesis of POP and new targets for treatment.
2022-09-05 | GSE208264 | GEO
Project description:Pelvic organ prolapse (POP) is a common multifactorial disease in a heterogeneous population of women. Due to this heterogeneity, the underlying molecular mechanisms contributing to the pathogenesis of POP are still unclear. We sought to identify dysregulated pathways by comparing gene expression profiles of prolapsed and non- prolapsed anterior vaginal wall tissue within the same patient. Biopsies were collected from 12 premenopausal women undergoing prolapse surgery (cystocele POP-Q stage ≥ 2). A full thickness anterior vaginal wall sample was taken from the POP site during anterior colporrhaphy. An additional sample was taken from the non-prolapsed apex of the anterior vaginal cuff. Micro-array analysis was performed using whole genome GE 4x44K microarrays. Beside a significance analysis of micro-array (SAM), also a visual cluster analysis was performed. 12 women with POP: 12 biopsies anterior vaginal wall (POP site) versus 12 biopies precervical anterior vaginal wall ( non POP site)
2015-07-31 | E-GEOD-53868 | biostudies-arrayexpress
Project description:Pelvic organ prolapse (POP) affects a large proportion of adult women. With the increase in global population ageing, the prevalence of POP is expected to increase in upcoming decades, which will impose a substantial medical burden. Therefore, suitable therapeutical target is important. However, due to the pathogenesis of POP is still unclear, it leads to the failure of POP repair. Herein, we identified changes in ncRNA, and mRNAs in the anterior vaginal wall and uterosacral ligament in patients with POP, providing new insights into the pathogenesis of POP and new targets for treatment.
2022-09-05 | GSE208261 | GEO
Project description:Introduction and Hypothesis: Identify processes contributing to pelvic organ prolapse (POP) by transcriptional profiling of pelvic connective tissue in conjunction with light microscopy. Methods: We performed a frequency matched case-control study of women undergoing hysterectomy. Total RNA, extracted from uterosacral and round ligament samples used to generate labeled cRNA, was hybridized to microarrays and analyzed for the expression of 32,878 genes. Significance Analysis of Microarrays, (Stanford University, CA), identified differentially expressed genes used for ontoanalysis, and quantitative PCR (qPCR) confirmed results. Light microscopy confirmed tissue type and assessed inflammatory infiltration. Results: The analysis of thirty-four arrays revealed 249 differentially expressed genes with fold changes larger than 1.5 fold and false discovery rates ≤5.2%. Immunity and Defense was the most significant biological process differentially expressed in POP. Selected qPCR confirmed 4 genes. Light microscopy showed no inflammatory infiltrates. Conclusions: Genes enriched for Immunity and Defense contribute to POP independent of inflammatory infiltrates. Keywords: whole tissue (endopelvic fascia) type comparison
2008-09-20 | GSE12852 | GEO
Project description:Pelvic organ prolapse (POP) markedly affects the quality of life of women, including significant financial burden. Using single-cell RNA sequencing, we constructed a transcriptional profile of 30,452 single cells of the uterosacral ligament in POP and control samples for the first time, and identified 10 major cell types, including smooth muscle cells, endothelial cells, fibroblasts, neutrophils, macrophages, monocytes, mast cells, T cells, B cells, and dendritic cells. We performed subpopulation analysis and pseudo-time analysis of POP primary cells, and explored differentially expressed genes. We verified previous cell clusters of human neutrophils of uterosacral ligaments. We found a significant reduction in receptor-ligand pairs related to ECM and cell adhesion between fibroblasts and endothelial cells in POP. The transcription factors related to the extracellular matrix, development, and immunity were identified in USL. Here we provide insight into the molecular mechanisms of POP and valuable information for future research directions.
2024-02-14 | GSE250414 | GEO
Project description:Transcriptomics analysis of gene expression in pelvic organ prolapse and control sample
| PRJNA635085 | ENA
Project description:<p>The overall purpose of this University of Utah Pelvic Organ Prolapse Disorder Study was to identify and localize predisposition genes contributing to pelvic organ prolapse (POP). POP cases recruited for this study were identified by one of three methods: high-risk POP pedigree cases, POP sister pairs, and surgically-treated POP cases reporting a family history of POP. <b>High-risk POP pedigree cases</b> were identified using the Utah Population Database (UPDB), a genealogy database of residents in Utah that has been linked to diagnostic ICD9 and CPT codes in medical records at the University of Utah and Intermountain Healthcare. We identified families with a significant excess number of POP cases compared to matched population rates and targeted these individuals for recruitment as well as any other POP cases in the family. <b>POP sister pair cases</b> were identified at the University of Utah Urogyncology clinic for women who had undergone POP surgery and also self-reported one or more sisters who were also surgically treated for POP. POP affection status of all sisters was confirmed either by physical examination or by chart review. <b>Surgically treated-POP cases reporting a family history of POP</b> were identified at the University of Utah Urogyncology clinic by self-report of a family history of POP. Efforts were made to recruit other affected family members and confirm affection status. To obtain DNA, subjects provided either a blood specimen or saliva. Medical records were reviewed by a urogynecologist and diagnostic information for pelvic organ prolapse and stress and overactive bladder were obtained. Collected DNA was genotyped and analyzed. To maintain confidentiality of the familial data, genetic data from only one subject per family has been submitted to dbGaP.</p> <p>Use of the University of Utah Pelvic Organ Prolapse Disorder Study data is limited to investigators studying pelvic floor disorders. These pelvic floor disorders include pelvic organ prolapse, urinary and anal incontinence, and other conditions related to weakening or injury to the muscles and connective tissue in the pelvis as a result of pelvic surgery, pregnancy, or vaginal delivery of a child. These data will be used only for research purposes related to pelvic floor disorders. They will not be used to determine the individual identity of any person or their relationship to another person or for research on non-disease traits.</p>
| phs001439 | dbGaP
Project description:Pelvic organ prolapse (POP) is a common multifactorial disease in a heterogeneous population of women. Due to this heterogeneity, the underlying molecular mechanisms contributing to the pathogenesis of POP are still unclear. We sought to identify dysregulated pathways by comparing gene expression profiles of prolapsed and non- prolapsed anterior vaginal wall tissue within the same patient. Biopsies were collected from 12 premenopausal women undergoing prolapse surgery (cystocele POP-Q stage ≥ 2). A full thickness anterior vaginal wall sample was taken from the POP site during anterior colporrhaphy. An additional sample was taken from the non-prolapsed apex of the anterior vaginal cuff. Micro-array analysis was performed using whole genome GE 4x44K microarrays. Beside a significance analysis of micro-array (SAM), also a visual cluster analysis was performed.
2015-07-31 | GSE53868 | GEO