MiRNA profiling in primary human peritoneal mesothelial cells (HPMCs) and TGF-β1-stimulated
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE79006 | GEO | 2017/04/05
SECONDARY ACCESSION(S): PRJNA381562
REPOSITORIES: GEO
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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
Project description:Long-term peritoneal dialysis is associated with progressive fibrosis of the peritoneum. Epithelial-mesenchymal transition (EMT) of mesothelial cells is an important mechanism involved in peritoneal fibrosis, and TGF-b1 is considered central in this process. We conducted network-based integrated analysis of transcriptomic data to systemically characterize the molecular signature of TGF-b1-stimulated human peritoneal mesothelial cells (HPMCs).
2018-10-18 | GSE121372 | GEO
Project description:Despite their emerging relevance to fully understand disease pathogenesis, we have as yet a poor understanding as to how biomechanical signals are integrated with specific biochemical pathways to determine cell behaviour. Mesothelial-to-mesenchymal transition (MMT) markers colocalized with TGF-beta1-dependent signalling and yes-associated protein (YAP) activation across biopsies from different pathologies exhibiting peritoneal fibrosis, supporting mechanotransduction as a central driving component of these class of fibrotic lesions and its crosstalk with specific signaling pathways. Transcriptome and proteome profiling of the response of mesothelial cells (MCs) to linear cyclic stretch revealed molecular changes compatible with bona fide MMT, which (i) overlapped with established YAP target gene subsets, and (ii) were largely dependent on endogenous TGF-beta1 signaling. Importantly, TGF-beta1 blockade blunts the transcriptional upregulation of the se gene signatures, but not the mechanical activation and nuclear translocation of YAP per se. We studied the role therein of caveolin-1 (Cav1), a plasma membrane mechanotransducer. Exposure of Cav1-deficient MCs to cyclic stretch led to a robust upregulation of MMT-related gene programs, which was blunted upon TGF-beta1 inhibition. Conversely, Cav1 depletion enhanced both TGF-beta1 and TGFBRI expression. Cav1 genetic deficiency exacerbated MMT and PA fibrosis in an experimental model of peritoneal ischaemic buttons. Taken together, these results support that Cav1-YAP/TAZ fine-tune the fibrotic response through the modulation of MMT, onto which TGF-beta1-dependent signaling coordinately converges. Our findings reveal a cooperation between biomechanical and biochemical signals in the triggering of MMT, representing a novel potential opportunity to intervene mechanically-induced disorders coursing with peritoneal fibrosis, such as post-surgical adhesions. This SuperSeries is composed of the SubSeries listed below.
2020-08-21 | GSE146955 | GEO
Project description:Peritoneal dialysis (PD) is an effective form of renal replacement therapy. A significant proportion of patients who initiate PD suffer from PD-related clinical complications, including peritoneal membrane damage, which may limit the duration of treatment. Mesothelial-to-mesenchymal transition (MMT) significantly contributes to the peritoneal dysfunction related to PD. Hence, we analyzed the genetic reprograming of the MMT-process with the aim to identify new biomarkers that may be tested in PD-patients. Microarray analysis revealed a partial overlapping of MMT induced in vitro and MMT of effluent-derived mesothelial cells (ex vivo), and that MMT, both in vitro and ex vivo, is mainly a repression process being higher the number of genes that are down-regulated than those that are induced. According to cellular morphology and the number of altered genes and pathways, the MMT ex vivo could be subdivided into two stages: early/epitheliod and advanced/non-epitheliod. We could demonstrate by RT-PCR array analysis that a number of genes differentially expressed in effluent-derived non-epitheliod cells also showed significant differential expression when comparing standard versus low-GDP PD fluids. Among the secreted proteins that are up-regulated along the MMT process thrombospondin-1 (TSP1), collagen-13 (COL13), vascular endothelial growth factor A (VEGFA), and gremlin-1 (GREM1) were selected to be measured in PD effluents. TSP1, COL13 and VEGFA, but not GREM1, showed significant differences between early and advanced stages of MMT, and their expression were associated with high peritoneal transport status. The results establish a proof of concept about the feasibility of MMT-associated secreted proteins as biomarkers in PD.
2017-03-22 | GSE92454 | GEO
Project description:Background: Malignant ascites is often present at diagnostic in women with advanced ovarian cancer (OC) and its presence is associated with a worse outcome. Human peritoneal mesothelial cells (HPMCs) are key components of malignant ascites. Although the interplay between HPMCs and OC cells is believed to be critical for tumor progression, it has not been well characterized. The purpose of this study was to assess the effect of ascites on HPMCs and clarify the role of HPMCs in OC progression. Methods: Human OC ascites and benign peritoneal fluids were assessed for their ability to stimulate HPMC proliferation. Conditioned medium from ascites- and benign fluid-stimulated HPMCs were compared for their ability to attenuate apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL). We conducted a comparative analysis of global expression changes in ascites-stimulated HPMCs using Agilent oligonucleotide microarrays. Results: As compared to benign peritoneal fluids, malignant ascites stimulated the proliferation of HPMCs. TRAIL-induced apoptosis was attenuated in OC cells exposed to conditioned medium from ascites-stimulated HPMCs as compared to OC cells exposed to conditioned medium from benign fluid-stimulated HPMCs. A total of 649 genes were differentially expressed in ascites-stimulated HPMCs. Based on a ratio of more than 1.5-fold and a P < 0.05, 484 genes were up-regulated and 165 genes were down-regulated in ascites-exposed HPMCs. Stimulation of HPMCs with OC ascites resulted in differential expression of genes mainly associated with the regulation of cell growth and proliferation, cell death, cell cycle and cell assembly and organization, compared to benign peritoneal fluids. Top networks up-regulated by OC ascites included Akt and NF-M-NM-:B survival pathways whereas vascular endothelial growth factor (VEGF) pathway was down-regulated. Conclusions: The results of this study not only provide evidence supporting the importance of the interplay between cancer cells and HPMCs but also define the role that the tumor environment plays in these interactions. The expression profiles from human peritoneal mesothelial cells (HPMC) cultures exposed to peritoneal fluids and ovarian cancer ascites were compared using the Agilent Whole Human Genome Oligonucleotide microarrays, containing 44,000 genes. Microarrays were performed on HPMCs exposed to 3 malignant ascites from women with advanced (stage III/IV) serous OC and two benign peritoneal fluids. First, we generated lists of significantly up-regulated and down-regulated genes that were differentially expressed between OC ascites (OVC346, OVC508 and OVC509) and control OV370 peritoneal fluid. Then, the set of genes that were commonly expressed between control peritoneal fluids (OV370 and OV401) were subtracted from the first list of genes to generate a dataset of differentially expressed genes between malignant ascites and benign peritoneal fluids.
2014-04-14 | E-GEOD-55065 | biostudies-arrayexpress
Project description:miRNA profiling in primary human peritoneal mesothelial cells (HPMCs) and TGF-β1-stimulated
| PRJNA381562 | ENA
Project description:These data show that the genes that distinguish myofibroblasts from fibroblasts are myriad, and that some genes not traditionally associated with myofibroblast differentiation may serve as novel therapeutic targets for fibrosing disorders. Gene expression levels were assessed from total RNA on the Affymetrix U219 microarray. Here, we use transforming growth factor-β1 (TGF-β1) and prostaglandin E2 (PGE2), which has recently been shown to reverse myofibroblast differentiation, to investigate the transcriptomic changes that occur during TGF-β1-induced differentiation and PGE2-induced de-differentiation of myofibroblasts.
2015-06-30 | E-GEOD-63659 | biostudies-arrayexpress
Project description:Fushen Granule (FSG), a Chinese medicinal formular, was clinically used to improve the peritoneal dialysis (PD) efficiency in ESRD patients received PD treatment. However, its mechanisms of anti-fibrotic effect in peritoneal fibrosis (PF) has not been studied yet. In this work, we used TGF-β1-stimulated MeT5A cells to mimic the process of PF in vitro, and Label-free proteomics and bioinformatics analysis were used to explored the underlying targets and pathways of FSG on TGF-β1-treated MeT5A cells
2022-04-20 | PXD033058 | Pride
Project description:Background: Malignant ascites is often present at diagnostic in women with advanced ovarian cancer (OC) and its presence is associated with a worse outcome. Human peritoneal mesothelial cells (HPMCs) are key components of malignant ascites. Although the interplay between HPMCs and OC cells is believed to be critical for tumor progression, it has not been well characterized. The purpose of this study was to assess the effect of ascites on HPMCs and clarify the role of HPMCs in OC progression. Methods: Human OC ascites and benign peritoneal fluids were assessed for their ability to stimulate HPMC proliferation. Conditioned medium from ascites- and benign fluid-stimulated HPMCs were compared for their ability to attenuate apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL). We conducted a comparative analysis of global expression changes in ascites-stimulated HPMCs using Agilent oligonucleotide microarrays. Results: As compared to benign peritoneal fluids, malignant ascites stimulated the proliferation of HPMCs. TRAIL-induced apoptosis was attenuated in OC cells exposed to conditioned medium from ascites-stimulated HPMCs as compared to OC cells exposed to conditioned medium from benign fluid-stimulated HPMCs. A total of 649 genes were differentially expressed in ascites-stimulated HPMCs. Based on a ratio of more than 1.5-fold and a P < 0.05, 484 genes were up-regulated and 165 genes were down-regulated in ascites-exposed HPMCs. Stimulation of HPMCs with OC ascites resulted in differential expression of genes mainly associated with the regulation of cell growth and proliferation, cell death, cell cycle and cell assembly and organization, compared to benign peritoneal fluids. Top networks up-regulated by OC ascites included Akt and NF-κB survival pathways whereas vascular endothelial growth factor (VEGF) pathway was down-regulated. Conclusions: The results of this study not only provide evidence supporting the importance of the interplay between cancer cells and HPMCs but also define the role that the tumor environment plays in these interactions.
2014-04-14 | GSE55065 | GEO
Project description:Peritoneal dialysis (PD) is an effective form of renal replacement therapy. A significant proportion of patients who initiate PD suffer from PD-related clinical complications, including peritoneal membrane damage, which may limit the duration of treatment. Mesothelial-to-mesenchymal transition (MMT) significantly contributes to the peritoneal dysfunction related to PD. Hence, we analyzed the genetic reprograming of the MMT-process with the aim to identify new biomarkers that may be tested in PD-patients. Microarray analysis revealed a partial overlapping of MMT induced in vitro and MMT of effluent-derived mesothelial cells (ex vivo), and that MMT, both in vitro and ex vivo, is mainly a repression process being higher the number of genes that are down-regulated than those that are induced. According to cellular morphology and the number of altered genes and pathways, the MMT ex vivo could be subdivided into two stages: early/epitheliod and advanced/non-epitheliod. We could demonstrate by RT-PCR array analysis that a number of genes differentially expressed in effluent-derived non-epitheliod cells also showed significant differential expression when comparing standard versus low-GDP PD fluids. Among the secreted proteins that are up-regulated along the MMT process thrombospondin-1 (TSP1), collagen-13 (COL13), vascular endothelial growth factor A (VEGFA), and gremlin-1 (GREM1) were selected to be measured in PD effluents. TSP1, COL13 and VEGFA, but not GREM1, showed significant differences between early and advanced stages of MMT, and their expression were associated with high peritoneal transport status. The results establish a proof of concept about the feasibility of MMT-associated secreted proteins as biomarkers in PD.
2017-03-22 | GSE92453 | GEO