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Intraperitoneal microbial contamination drives post-surgical peritoneal adhesions by mesothelial EGFR-signaling.

ABSTRACT: Intraperitoneal microbial contamination drives post-surgical peritoneal adhesions by mesothelial EGFR-signaling.

PROVIDER: PRJNA774989 | ENA |

REPOSITORIES: ENA

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Intraperitoneal microbial contamination drives post-surgical peritoneal adhesions by mesothelial EGFR-signaling.

Project description:Abdominal surgeries are lifesaving procedures but can be complicated by the formation of peritoneal adhesions, intra-abdominal scars that cause intestinal obstruction, pain, infertility, and significant health costs. Despite this burden, the mechanisms underlying adhesion formation remain unclear and no cure exists. Here, we show that contamination of gut microbes increases post-surgical adhesion formation. Using genetic lineage tracing we show that adhesion myofibroblasts arose from the mesothelium. This transformation was driven by epidermal growth factor receptor (EGFR) signaling. The EGFR ligands Amphiregulin and Heparin-binding Epidermal Growth Factor, were sufficient to induce these changes. Correspondingly, EGFR inhibition led to a significant reduction of adhesion formation in mice. Adhesions isolated from human patients were enriched in EGFR positive cells of mesothelial origin and human mesothelium showed an increase of mesothelial EGFR expression during bacterial peritonitis. In conclusion, bacterial contamination drives adhesion formation through mesothelial EGFR signaling. This mechanism may represent a therapeutic target for the prevention of adhesions after intra-abdominal surgery.

2021-11-08 | GSE186658 | GEO

Intraperitoneal microbial contamination drives post-surgical peritoneal adhesions by mesothelial EGFR-signaling.

Project description: Not available

| S-EPMC8677808 | biostudies-literature

Transcriptome analysis of mesothelial cells induced by intraperitoneal injections of crocidolite in rats

Project description:Malignant mesothelioma (MM) is an aggressive tumor strongly associated with asbestos exposure. The granuloma capturing crocidolite contribute to mutagenesis, cell death and regenerative activity. To clarify the biological responses of mesothelial cells after crocidolite exposure, we compared the microarray gene expression profiles of no treatment and crocidolite exposure (1 wks) mesothelial cells induced by intraperitoneal injections.

2020-06-26 | GSE149285 | GEO

Gene expression differences in omental mesothelial cells from lean and obese human donors

Project description:Visceral adipose tissue inflammation correlates with metabolic dysfunction in obesity. However, critical cell types that trigger and contribute to inflammation in this depot are not completely understood. Mesothelial cells line the omental fat depot and are thought to contribute to several intraperitoneal inflammatory conditions. Whether adipose-associated mesothelial cell inflammation is a feature of pathologic obesity is unclear. This study was performed to delineate a contribution of omental adipose mesothelial cells to visceral adipose tissue dysfunction in pathologic obesity. We performed a cross-sectional case-control study from two separate cohorts of patients undergoing abdominal surgery with varying degrees of obesity and metabolic disease. Whole-genome expression profiling was conducted on mesothelial cells isolated from lean and obese surgical patients to determine differences in relevant pathways related to obesity and metabolic disease.

2019-03-08 | GSE128021 | GEO

Next generation sequencing of changes in mesothelial transcriptome post-surgery

Project description:Purpose: The goal of this study was to investigate post-surgical transcriptomic changes in mesothelial cells Methods: Mesothelial cells were immonopurified using anti-glycoprotein M6A antibody.

2021-11-08 | GSE156127 | GEO

Transcriptome analysis of mesothelial cells induced by intraperitoneal injections of crocidolite in rats

Project description:Transcriptome analysis of mesothelial cells induced by intraperitoneal injections of crocidolite in rats

| PRJNA627903 | ENA

Expression data from FedEV uptake mesothelial cells

Project description:Asbestos-associated diseases remain a social burden worldwide. Our previous studies identified asbestos-induced iron-rich milieu for mesothelial cells with ceaseless macrophage ferroptosis. However, molecular mechanisms how this mutagenic milieu influences mesothelial cells have not been elucidated yet. Here, we propose a novel mechanism that extracellular vesicles (EVs) mediate asbestos-associated mutagenic factors to mesothelial cells. In a mice model of intraperitoneal crocidolite injection, mutagenic milieu highly expressed CD63, an exosomal marker. We then used a CD63-GFP labeled THP-1 macrophage model exposed to crocidolite/iron, which generated EVs under ferroptotic process. We observed that MeT-5A mesothelial cells can receive and internalize these EVs. Furthermore, we comprehensively analyzed the ferroptosis-dependent EVs (FedEVs) for transported proteins and identified ferritin heavy/light chains as major proteins. Therefore, we inferred that FedEVs transport iron from ferroptotic macrophages to mesothelial cells. RNA sequencing revealed that the mesothelial cells receiving higher amounts of the FedEVs were mitotic, especially at the S and G2/M phases, by the use of Fucci mesothelial cells. Nuclear 8-hydroxy-2`-deoxyguanosine and γ-H2AX were significantly increased in the recipient mesothelial cells after exposure to FedEVs. Collectively, we here demonstrate a novel mechanism that FedEVs act as a key mutagenic mediator by transporting iron, which contribute to asbestos-induced mesothelial carcinogenesis.

2021-10-22 | GSE184368 | GEO

Whole transcriptome analysis of rat peritoneal cells in a TGFβ1 induced mesothelial-to-mesenchymal transition

Project description:Peritoneal fibrosis is a major complication of long-term peritoneal dialysis (PD), leading to ultrafiltration failure and sometimes life threatening encapsulating peritoneal sclerosis. Fibrosis is driven by activated myofibroblasts that are derived, in part, from mesothelial-to-mesenchymal transition (MMT). We aimed to discover novel mediators of MMT and then experimentally exploit them to prevent peritoneal fibrosis. Using an antibody to HBME-1 and streptavidin nanobead technology, we first pioneered a novel method to purify rat mesothelial cells. After exposing mesothelial cells to transforming growth factor β1 (TGFβ1), we undertook RNAseq whole transcriptome analyses and outlined, the expression profile of sorted mesothelial cells at pre- and post- MMT.

2018-06-18 | E-MTAB-5998 | biostudies-arrayexpress

Microarray analysis of primary human peritoneal mesothelial cells derived from omentum

Project description:Peritoneal mesothelial cells are harmed by peritoneal dialysis fluids (PDF) used in renal replacement therapy with peritoneal dialysis. The mechanisms of the cellular damage are not yet described in detail. Primary human peritoneal mesothelial cells derived from omentum of five donors were independently exposed to peritoneal dialysis fluids (extended recovery time). The extent of cell damage was assessed using lactate dehydrogenase (LDH) release in the cell culture supernatant and cells were lysed in order to extract mRNA and proteins. Transcriptional changes induced by PDF were analyzed using gene expression microarrays and changes of the proteome were analyzed using 2D-electrophoresis.

2019-12-31 | E-MTAB-7793 | biostudies-arrayexpress

Microarray analysis of primary human peritoneal mesothelial cells derived from omentum

Project description:Peritoneal mesothelial cells are harmed by peritoneal dialysis fluids (PDF) used in renal replacement therapy with peritoneal dialysis. The mechanisms of the cellular damage are not yet described in detail. Primary human peritoneal mesothelial cells derived from omentum of five donors were independently exposed to peritoneal dialysis fluids. The extent of cell damage was assessed using lactate dehydrogenase (LDH) release in the cell culture supernatant and cells were lysed in order to extract mRNA and proteins. Transcriptional changes induced by PDF were analyzed using gene expression microarrays and changes of the proteome were analyzed using 2D-electrophoresis.

2019-12-31 | E-MTAB-7485 | biostudies-arrayexpress

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