Multi-Omics Integration Highlights the Role of Ubiquitination in Endometriosis Fibrosis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE212787 | GEO | 2024/05/12
REPOSITORIES: GEO
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Project description:In this study, we comprehensively profiled the ubiquitination landscape of endometriosis for the first time. Through proteomics, transcriptomics, and ubiquitylomics analyses of endometrial tissues from two patient cohorts, we uncovered significant dysregulation of ubiquitin-related enzymes and ubiquitinated proteins. By comparing tissues in pathological and healthy states, we delineated ubiquitinated proteins associated with the etiology of endometriosis and revealed their regulatory roles in relevant biological processes. We observed a pivotal role of ubiquitination in the fibrotic process, particularly in processes related to the activity of myofibroblasts and collagen deposition in ectopic tissues. Besides, we uncovered the downregulation of the E3 ubiquitin ligase TRIM33 in endometriotic tissues, along with its negative regulatory effect on fibrosis-related proteins TGFBR1/p-SMAD2/α-SMA/FN1 in vitro. It is important to note that, while our study provides compelling evidence supporting the crucial role of ubiquitination in endometriosis and the negative regulatory effect of TRIM33 on fibrosis, the specific regulatory mechanisms require further in-depth functional studies. This study contributes to a deeper understanding of endometriosis pathogenesis and highlights the potential of targeting ubiquitination pathways for therapeutic intervention in this debilitating condition.
2024-04-09 | PXD036497 |
Project description:Multi-Omics Integration Highlights the Role of Ubiquitination in Endometriosis Fibrosis
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Project description:We primary cultured ectopic endometrial cells from patients with endometriosis (2 cases) and without endometriosis(2 cases) and collected cell culture supernatants（P0). We isolated exosomes from cell culture supernatants by differential centrifugation and then performed proteome analysis on the two groups of exosomes to investigate the role of ectopic endometrial cell-derived exosomes in the development of endometriosis.
2022-06-09 | PXD033124 | Pride
Project description:Alterations in endometrial DNA methylation profile have been proposed as one potential mechanism initiating the development of endometriosis. However, the normal endometrial methylome is influenced by the cyclic hormonal changes and the menstrual cycle phase-dependent epigenetic signature should be considered when studying endometrial disorders. So far, no studies have been performed to evaluate the menstrual cycle influences and endometriosis-specific endometrial methylation pattern at the same time. Therefore, we used Infinium HumanMethylation 450K BeadChip arrays to explore DNA methylation profiles of endometrial tissues from various menstrual cycle phases. Infinium HumanMethylation 450K BeadChip arrays were used to explore DNA methylation profiles of endometrial tissues from mid secretory cycle phase from 17 patients without endometriosis
2016-02-15 | E-GEOD-73949 | biostudies-arrayexpress
Project description:Alterations in endometrial DNA methylation profile have been proposed as one potential mechanism initiating the development of endometriosis. However, the normal endometrial methylome is influenced by the cyclic hormonal changes and the menstrual cycle phase-dependent epigenetic signature should be considered when studying endometrial disorders. So far, no studies have been performed to evaluate the menstrual cycle influences and endometriosis-specific endometrial methylation pattern at the same time. Therefore, we used Infinium HumanMethylation 450K BeadChip arrays to explore DNA methylation profiles of endometrial tissues from various menstrual cycle phases. Infinium HumanMethylation 450K BeadChip arrays were used to explore DNA methylation profiles of endometrial tissues from various menstrual cycle phases from 24 patients with endometriosis
2016-02-15 | E-GEOD-73948 | biostudies-arrayexpress
Project description:Liver fibrosis is the excessive accumulation of extracellular matrix proteins that occurs in chronic liver disease. Ubiquitination is a post-translational modification that is crucial for a plethora of physiological processes. Even though the ubiquitin system has been implicated in several human diseases, the role of ubiquitination in liver fibrosis remains poorly understood. Here, multi-omics approaches were used to address this. Untargeted metabolomics showed that carbon tetrachloride (CCl4)-induced liver fibrosis promotes changes in the hepatic metabolome, specifically in glycerophospholipids and sphingolipids. Gene ontology analysis of public deposited gene array-based data and validation in our mouse model showed that the biological process "protein polyubiquitination" is enriched after CCl4-induced liver fibrosis. Finally, by using transgenic mice expressing biotinylated ubiquitin (bioUb mice), the ubiquitinated proteome was isolated and characterized by mass spectrometry in order to unravel the hepatic ubiquitinated proteome fingerprint in CCl4-induced liver fibrosis. Under these conditions, ubiquitination appears to be involved in the regulation of cell death and survival, cell function, lipid metabolism, and DNA repair. Finally, ubiquitination of proliferating cell nuclear antigen (PCNA) is induced during CCl4-induced liver fibrosis and associated with the DNA damage response (DDR). Overall, hepatic ubiquitome profiling can highlight new therapeutic targets for the clinical management of liver fibrosis.
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Project description:Endometriosis is a leading cause of pain and infertility affecting millions of women globally. Biological and genetic effects on DNA methylation (DNAm) can influence gene regulation and contribute to complex disease. Herein, we characterize variation in endometrial DNAm and its association with menstrual cycle phase, endometriosis, and genetic variants through analysis of genome-wide genotype data and methylation at 759,345 DNAm sites in endometrial samples from 984 deeply-phenotyped participants. We estimate that 15.4% of the variation in endometriosis is captured by DNAm and identify significant differences in DNAm profiles and DNAm networks, associated with endometriosis, endometriosis sub-phenotypes and menstrual cycle phase, including opening of the window for embryo implantation. DNAm quantitative trait locus (mQTL) analysis identified 118,185 independent cis-mQTLs including 51 associated with risk of endometriosis highlighting candidate genes contributing to disease risk. Our work provides functional evidence for epigenetic targets contributing to endometriosis risk and pathogenesis. Data generated serve as a valuable resource for understanding tissue-specific effects of methylation on endometrial biology in health and disease.
2023-09-12 | GSE223817 | GEO
Project description:Endometriosis is a common disease seen by gynecologists. Clinical features involve pelvic pain and unexplained infertility. Although endometriosis is pathologically characterized by endometrial tissue outside the normal uterine location, endometriosis is otherwise not easily explained. Endometriomas, endometriotic cysts of the ovary, typically cause pain and distortion of pelvic anatomy. To begin to understand the pathogenesis of endometriomas, we carried out transcriptome:microRNAome analysis of endometriomas and eutopic endometrium, using gene expression arrays and next generation small RNA sequencing technology. Keywords: two group comparison Patients undergoing surgery for endometriomas, suspected endometriosis, pelvic pain, abnormal uterine bleeding, pelvic organ prolapse, or uterine leiomyomas were approached for participation. After informed consent, the patients underwent scheduled surgical procedure. Tissues were collected either as cyst wall of endometrioma or endometrial curettage of hysterectomy specimen and placed directly into RNALater (Ambion, Austin, TX) and eventually frozen at -80?C. Samples were designated as endometriomas or non-endometriosis control endometrium based on surgical pathology reports. Total RNA was isolated from frozen tissue. High quality RNA was subjected to Illumina’s Human WG-6 version 2.0 BeadChips (Illumina). . *** This Series represents the transcriptome component of the study. ***
2011-05-09 | E-GEOD-23339 | biostudies-arrayexpress
Project description:Alterations in endometrial DNA methylation profile have been proposed as one potential mechanism initiating the development of endometriosis. However, the normal endometrial methylome is influenced by the cyclic hormonal changes and the menstrual cycle phase-dependent epigenetic signature should be considered when studying endometrial disorders. So far, no studies have been performed to evaluate the menstrual cycle influences and endometriosis-specific endometrial methylation pattern at the same time. Therefore, we used Infinium HumanMethylation 450K BeadChip arrays to explore DNA methylation profiles of endometrial tissues from various menstrual cycle phases.
2016-02-15 | GSE73949 | GEO
Project description:Alterations in endometrial DNA methylation profile have been proposed as one potential mechanism initiating the development of endometriosis. However, the normal endometrial methylome is influenced by the cyclic hormonal changes and the menstrual cycle phase-dependent epigenetic signature should be considered when studying endometrial disorders. So far, no studies have been performed to evaluate the menstrual cycle influences and endometriosis-specific endometrial methylation pattern at the same time. Therefore, we used Infinium HumanMethylation 450K BeadChip arrays to explore DNA methylation profiles of endometrial tissues from various menstrual cycle phases.
2016-02-15 | GSE73948 | GEO