Microvascular Permeability, Inflammation, and Lesion Physiology in Endometriosis: A Microphysiological Systems Approach
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PROVIDER: PRJNA987021 | ENA |
REPOSITORIES: ENA
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Project description:Microvascular Permeability, Inflammation, and Lesion Physiology in Endometriosis: A Microphysiological Systems Approach
| PRJNA987020 | ENA
Project description:Acute respiratory distress syndrome (ARDS) is a leading cause of intensive care unit (ICU) admissions and is associated with high short- and long-term mortality, particularly among elderly patients. Aging is a major risk factor for ARDS development and worsened outcomes, yet the mechanisms underlying age-related susceptibility remain poorly defined. Pulmonary microvascular endothelial cell (PMVEC) barrier dysfunction plays a central role in ARDS pathophysiology, where disruption of cell-cell junctions leads to increased vascular permeability and alveolar edema. While aging has been associated with increased microvascular permeability in several vascular beds, the specific effects of age on pulmonary endothelial cell junctions remain largely unexplored. Here, we investigated the impact of aging on PMVEC barrier function and junctional integrity under basal conditions. Using the XperT permeability assay, we demonstrate that PMVECs from aged mice exhibit significantly increased paracellular leak and disrupted VE-cadherin localization compared to those from young mice. Western blot analyses further revealed age-associated reductions in the tight junction protein claudin-5 and the adherens junction protein γ-catenin, despite an increase in VE-cadherin levels. Proteomic profiling of PMVECs uncovered broad age-related differences in pathways related to mRNA processing, protein folding, cytoskeletal regulation, and inflammation. These findings suggest that aging impairs pulmonary endothelial barrier integrity through cell junction disruption and proteome remodeling, offering mechanistic insight into the heightened vulnerability of elderly individuals to ARDS. Targeting age-associated endothelial dysfunction may represent a promising therapeutic strategy to mitigate ARDS morbidity and mortality in aging populations
2025-12-29 | PXD065409 | Pride
Project description:Ultra-Processed Foods drive Intestinal Barrier permeability increasing Microvascular Disease risk
| PRJNA596437 | ENA
Project description:Endometriosis shows significant lesion heterogeneity, but pathophysiological mechanisms leading to differences in clinical presentation are poorly understood. Here we utilized primary stromal cells from different types of endometriotic lesions to better understand the molecular mechanisms that lead to endometriosis heterogeneity. For this project, endometrial stromal cells (ESCs) were obtained from eutopic endometrium (EU), endometrioma (OMA), superficial (SF) and deep (DE) endometriosis lesions and analyzed in vitro for their behavior regarding proliferation, migration, and contractility. RNA sequencing was performed to explore the molecular mechanism underlying the observed changes.
2025-12-17 | GSE303635 | GEO
Project description:Our understanding of molecular mechanisms contributing to the pathophysiology of endometriosis, and their upstream regulators, remains limited. Using a C57Bl/6 mouse model of endometriosis in which decidualized endometrial tissue fragments are transferred to subcutaneous sites in recipient mice to mimic endometriosis lesions, we have generated a comprehensive profile of gene expression in decidualized endometrial tissue (n=4), and endometriosis-like lesions at Day 7 (n=4) and Day 14 (n=4) of lesion formation. High throughput mRNA sequencing allowed identification of genes and pathways involved in the initiation and progression of endometriosis-like lesions. We found distinct patterns of gene expression with substantial differences between the lesions and the decidualized endometrium from which they arose, but no differentially expressed genes between the two lesion timepoints. The transcriptional changes at the outset of lesion formation indicated substantial upregulation of immune response-associated canonical pathways. Pathway enrichment analysis indicates multiple potential endogenous upstream regulators, and reveals multiple gene candidates not previously implicated in endometriosis lesion formation suggesting these mediators may have novel roles in disease progression. Collectively, the provided data will be a valuable resource to inform research on the molecular mechanisms contributing to endometriosis development.
2024-10-17 | GSE255418 | GEO
Project description:We performed gene expression analysis human peritoneal endometriosis lesions, eutopic endometrium from endometriosis patients and peritoneum form endometriosis patients.The goal of the study was to analyse gene expression differences between peritoneal endometriosis lesion and eutopic endometrium and peritoneal endometriosis lesion and peritoneum.
2012-12-06 | E-MTAB-694 | biostudies-arrayexpress
Project description:Endometriosis is a debilitating and painful gynecological inflammatory disease affecting approximately 15% of women. Current treatments are ineffective for a significant fraction of patients, underscoring the need for new medical therapies with long-term benefits. Given the relevance of neuroimmune communication in different disease outcomes, we investigated the role of CGRP-mediated neuroimmune communication in endometriosis. We found that mouse and human endometriosis lesions contained CGRP and RAMP1. In mice, nociceptor ablation reduced pain, monocyte recruitment, and lesion size, suggesting that nociceptor activation and neuropeptide release contribute to endometriosis lesion growth and pain. In vitro, CGRP-induced pro-endometriosis macrophages (PEMs) showed impaired efferocytosis and supported endometrial cell growth in a RAMP1-dependent manner. Treatment with FDA-approved drugs that block CGRP-RAMP1 signaling reduced mechanical hyperalgesia, spontaneous pain, and lesion size in mice. Altogether, our data demonstrates the effectiveness, cellular mechanisms and pre-clinical safety of non-hormonal and non-opioid CGRP/RAMP1 blocking therapies, which may lead to clinical benefit for endometriosis patients.
2025-08-09 | GSE274685 | GEO
Project description:Abstract: Our intake of ultra-processed foods has dramatically increased over the past few decades in line with the prevalence of obesity and diabetes, key risk factors for microvascular diseases such as chronic kidney disease (CKD). The extent to which long-term intake of highly processed food influences CKD outcome is unclear. Here, we show in rodent models that a highly processed diet drives intestinal barrier permeability and an increased risk of CKD. Inhibition of the advanced glycation pathway, which generates Maillard reaction products within foods upon thermal processing, reversed kidney injury. Consequently, a highly processed diet leads to innate immune complement activation and local kidney inflammation via the potent proinflammatory effector molecule complement 5a (C5a). C5a receptor inhibition ameliorated albuminuria. In a mouse model of diabetes, a high resistant starch fiber diet led to a redistribution of the gut commensal consortium, prevented impaired gut barrier function and decreased the severity of kidney injury via suppression of complement. These results provide mechanistic insight into the role of highly processed foods on inflammation and chronic disease risk. One Sentence Summary: Ultra-processed diets promote chronic kidney disease
2020-12-18 | GSE142261 | GEO
Project description:This project aims at comparing endometrium from women with and without endometriosis during the secretory phase of menstrual cycle. The present results constitute a first step towards identifying potential diagnosis biomarkers and may provide a better understanding of endometriosis especially the etiology of the disease.
2022-04-01 | PXD012981 | Pride
Project description:The effect of neuronal activity on blood-brain barrier function and whether it plays a role in plasticity in the healthy brain remains unclear. We show that neuronal activity induces modulation of microvascular permeability in the healthy brain and that it has a role in local network reorganization. Combining simultaneous electrophysiological recording and vascular imaging with transcriptomic analysis in rats, and functional and BBB-mapping MRI in human subjects we show that prolonged stimulation of the limb induces a focal increase in BBB permeability in the corresponding somatosensory cortex that is associated with long-term synaptic plasticity. We further show that the increased microvascular permeability depends on neuronal activity and involves caveolae-mediated transcytosis and transforming growth factor beta signaling. Our results reveal a role of BBB modulation in cortical plasticity in the healthy brain, highlighting the importance of neurovascular interactions for sensory experience and learning.
2024-01-31 | GSE223282 | GEO