Dataset Information

Human POP analysis - Proteomics of Uterosacral Ligament Connective Tissue from Women With and Without Pelvic Organ Prolapse

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Hai-Tao Pan

LAB HEAD: Xiang-Juan Li

PROVIDER: PXD011467 | Pride | 2018-12-10

REPOSITORIES: pride

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Proteomics of Uterosacral Ligament Connective Tissue from Women with and without Pelvic Organ Prolapse.

Li Xiang-Juan XJ Pan Hai-Tao HT Chen Juan-Juan JJ Fu Yi-Bin YB Fang Min M He Guo-Hua GH Zhang Tao T Ding Hai-Gang HG Yu Bin B Cheng Yi Y Tan Ya-Jing YJ Zhao Fa-Lin FL Morse Abraham N AN Huang He-Feng HF

Proteomics. Clinical applications 20181227 4

<h4>Purpose</h4>Damage to the uterosacral ligaments is an important contributor to uterine and vaginal prolapse. The aim of this study is to identify differentially expressed proteins (DEPs) in the uterosacral ligaments of women with and without pelvic organ prolapse (POP) and analyze their relationships to cellular mechanisms involved in the pathogenesis of POP.<h4>Experimental design</h4>Uterosacral ligament connective tissue from four patients with POP and four control women undergo iTRAQ ana ...[more]

PMID: 30516354

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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>

Project description:Periodontal regeneration study. Periodontitis is a common chronic inflammatory disease which may lead to tooth loss. The ultimate goal of periodontal therapy is complete regeneration of the tissues lost as a result of periodontitis. However, most regenerative clinical procedures are unpredictable, largely because there is a lack of understanding of how the various tissues comprising the periodontium (gingival epithelium, gingival connective tissue, periodontal ligament, aveolar bone and cementum) interact during the regenerative process. The aim of this study was to investigate the molecular mechanisms that are involved in periodontal regeneration. For this purpose, paired sets of gingival, ligament and regenerating cells were isolated from patients that have been treated for periodontitis via a regenerative surgical procedure. A microarray analysis using the Hu133A Affymetrix arrays was used to identify the genes and pathways that were characteristic of the three different tissues. We have identified over 500 transcripts in global comparison and intrapatient comparisons that were differentially expressed between ligament and gingival samples, and approximately 30 transcripts that characterized the regenerating cell population. By using a functional classification based on Gene Ontology we were able to group the transcripts into 12 groups. Proteases/Protease inhibitors were differentially expressed between the ligament and gingiva highlighting high ECM remodelling activity by gingival cells. On the other hand, ligament cells were shown to have increased protein synthesis by increasing their nucleolar and ribosomal gene complement. We were able to identify 57 various DNA binding proteins, among them were some well characterised transcription factors, transcriptional regulators, including DNA polymerases and transcriptional co-activators. Furthermore, we have also identified changes in expression of their targets in the two tissues. This is the first study to characterise the gene expression profile of periodontal regenerating cells and allowed us to gain valuable insights into the cellular and molecular mechanisms that occur during the regenerative process. We have identified signalling pathways which are consistent with clinical observations of the regenerative properties of gingival and periodontal ligament cells. These pathways provide candidate targets that can be manipulated in order to achieve a superior regenerative clinical outcome.

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Dataset Information

Human POP analysis - Proteomics of Uterosacral Ligament Connective Tissue from Women With and Without Pelvic Organ Prolapse

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Publications

Proteomics of Uterosacral Ligament Connective Tissue from Women with and without Pelvic Organ Prolapse.

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