Homo sapiens
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PROVIDER: PRJNA357607 | ENA |
REPOSITORIES: ENA
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Project description:Mesenchymal Transition in Human Mesothelial Cells In Vitro and Ex Vivo
| PRJNA357605 | ENA
Project description:CD4+ T cells that selectively produce interleukin (IL)-17, are critical for host defense and autoimmunity. Crucial for T helper17 (Th17) cells in vivo, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-β1 have been argued to be the factors responsible for initiating specification. Herein, we show that Th17 differentiation occurs in the absence of TGF-β signaling. Neither IL-6 nor IL-23 alone efficiently generated Th17 cells; however, these cytokines in combination with IL-1β effectively induced IL-17 production in naïve precursors, independently of TGF-β. Epigenetic modification of the Il17a/Il17f and Rorc promoters proceeded without TGF-β1, allowing the generation of cells that co-expressed Rorγt and T-bet. T-bet+Rorγt+ Th17 cells are generated in vivo during experimental allergic encephalomyelitis (EAE), and adoptively transferred Th17 cells generated with IL-23 in the absence of TGF-β1 were more pathogenic in this experimental disease. These data suggest a new model for Th17 differentiation. Consistent with genetic data linking the IL23R with autoimmunity, our findings re-emphasize the role of IL-23 and therefore have important implications for the development of new therapies. Examination of Stat3 binding and H3K4me and H3Ac in helper T cells.
2010-08-31 | E-GEOD-23681 | biostudies-arrayexpress
Project description:CD4+ T cells that selectively produce interleukin (IL)-17, are critical for host defense and autoimmunity1-4. Crucial for T helper17 (Th17) cells in vivo5,6, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-β1 have been argued to be the factors responsible for initiating specification7-10. Herein, we show that Th17 differentiation occurs in the absence of TGF-β signaling. Neither IL-6 nor IL-23 alone efficiently generated Th17 cells; however, these cytokines in combination with IL-1β effectively induced IL-17 production in naïve precursors, independently of TGF-β. Epigenetic modification of the Il17a/Il17f and Rorc promoters proceeded without TGF-β1, allowing the generation of cells that co-expressed Rorγt and T-bet. T-bet+Rorγt+ Th17 cells are generated in vivo during experimental allergic encephalomyelitis (EAE), and adoptively transferred Th17 cells generated with IL-23 in the absence of TGF-β1 were more pathogenic in this experimental disease. These data suggest a new model for Th17 differentiation. Consistent with genetic data linking the IL23R with autoimmunity, our findings re-emphasize the role of IL-23 and therefore have important implications for the development of new therapies. Mouse T helper 17 cell differentiation with or without TGFB
2010-08-31 | E-GEOD-23505 | biostudies-arrayexpress
Project description:TORAY microarray assays were performed on HPMCs derived from four independent donors. miRNA expression was measured in control samples and after 1 ng/ml of TGF-β1 treatment for 48 h. TGF-β1-driven mesothelial-to-mesenchymal transition (MMT) was confirmed in all samples by analysis of the eight molecular markers previously described (data not shown). A total of 1 μg in a volume of ≤2 μl of total RNA from each sample was subsequently used for Toray microarray analysis, performed by Central Biotechnology Services at Cardiff University.
2017-04-05 | GSE79006 | GEO
Project description:Mesenchymal Transition in Human Mesothelial Cells In Vitro and Ex Vivo [Epitheliod vs Non-Epitheliod]
| PRJNA357606 | ENA
Project description:Venkatraman2012 - Interplay between PLS and TSP1 in TGF-β1 activation
The interplay between PLS (Plasmin) and TSP1 (Thrombospondin-1) in TGF-β1 (Transforming growth factor-β1)is shown using mathematical modelling and in vitro
experimentents.
This model is described in the article:
Plasmin triggers a switch-like decrease in thrombospondin-dependent activation of TGF-β1.
Venkatraman L, Chia SM, Narmada BC, White JK, Bhowmick SS, Forbes Dewey C Jr, So PT, Tucker-Kellogg L, Yu H.
Biophys J. 2012 Sep 5;103(5):1060-8.
Abstract:
Transforming growth factor-β1 (TGF-β1) is a potent regulator of extracellular matrix production, wound healing, differentiation, and immune response, and is implicated in the progression of fibrotic diseases and cancer. Extracellular activation of TGF-β1 from its latent form provides spatiotemporal control over TGF-β1 signaling, but the current understanding of TGF-β1 activation does not emphasize cross talk between activators. Plasmin (PLS) and thrombospondin-1 (TSP1) have been studied individually as activators of TGF-β1, and in this work we used a systems-level approach with mathematical modeling and in vitro experiments to study the interplay between PLS and TSP1 in TGF-β1 activation. Simulations and steady-state analysis predicted a switch-like bistable transition between two levels of active TGF-β1, with an inverse correlation between PLS and TSP1. In particular, the model predicted that increasing PLS breaks a TSP1-TGF-β1 positive feedback loop and causes an unexpected net decrease in TGF-β1 activation. To test these predictions in vitro, we treated rat hepatocytes and hepatic stellate cells with PLS, which caused proteolytic cleavage of TSP1 and decreased activation of TGF-β1. The TGF-β1 activation levels showed a cooperative dose response, and a test of hysteresis in the cocultured cells validated that TGF-β1 activation is bistable. We conclude that switch-like behavior arises from natural competition between two distinct modes of TGF-β1 activation: a TSP1-mediated mode of high activation and a PLS-mediated mode of low activation. This switch suggests an explanation for the unexpected effects of the plasminogen activation system on TGF-β1 in fibrotic diseases in vivo, as well as novel prognostic and therapeutic approaches for diseases with TGF-β dysregulation.
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2024-09-02 | BIOMD0000000447 | BioModels
Project description:Endothelial-to-mesenchymal transition (EndMT) is a dynamic transformation process that has a functional impact upon pathological vascular remodelling. However, the molecular mechanisms that govern EndMT remain largely unknown. We modelled this process in vitro by exposing human primary endothelial cells to a combination of transforming growth factor-β2 (TGF- β2) and interleukin-1β (IL-1β). RNAseq was carried out to analyse the change of gene expression during the transition and define the transcriptional architecture of EndMT.
2020-12-31 | GSE118446 | GEO
Project description:Purpose: Fibroblast-like synoviocytes (FLSs) play a crucial role in maintaining joint homeostasis by secreting matrix components and lubricin [1, 2]. However, under inflammatory conditions, FLSs contribute to tissue damage, leading to osteoarthritis (OA) [3]. The specific genes and pathways driving this inflammatory response in FLSs remain poorly understood. This study aims to elucidate the transcriptome-wide responses of FLSs to IL-1β, a master proinflammatory cytokine, and to investigate the modulatory effects of TGF-β1 on the expression of chemokine transcripts in a model of inflammatory arthritis. Methods: Normal FLSs were isolated from synovial explants obtained from patients undergoing anterior cruciate ligament reconstruction surgery. The isolated cells were expended and exposed to IL-1β (10 ng/mL) for 24 hours to simulate inflammatory arthritis. Changes in gene expression were assessed by RNA-seq and validated through Fluidigm multiplex real-time PCR [4]. In a separate experiment, FLSs were pre-treated with IL-1β as above and subsequently exposed to TGF-β1 (10 ng/mL) for an additional 48 hours to evaluate its potential modulatory effects on the expression of chemokines as determined by Fluidigm multiplex real-time PCR. Results: IL-1β-treated FLSs showed a significant upregulation of numerous chemokines, including CCL20, CCL5, CXCL8, CXCL6, CXCL4, CXCL1, CXCL3, and CXCL2. Additionally, transcripts associated with inflammatory arthritis, such as CSF2, CSF3, MMP12, IL1B, and LIPM, were elevated (Table 1). Expression of KRT14, KRT19, KRT18, and several other anabolic and matrix genes was significantly reduced with IL-1β-treatment (Table 1). The genes highly expressed in IL-1β-treated cells were enriched for NFkB signaling, cytokine and chemokine signaling, TNF signaling, and necroptosis, whereas genes lowly expressed were enriched for the immune system. TGF-β1 treatment exhibited strong anti-inflammatory effects, modulating the expression of numerous chemokines and inflammatory mediators, thereby counteracting the IL-1β-induced inflammatory response in FLSs (Fig. 1). Moreover, the expression of the chemokine transcription factor C/EBPβ was also high (about twofold) in IL-1β-treated cells, which was reduced by half after TGF-β1 treatment, suggesting that TGF-β1 exerts its anti-chemokine effects through transcriptional repression of C/EBPβ in FLSs. Conclusions: This is the first study to examine the effects of IL-1β treatment in FLS derived from patients with ACL tears. Our data show that IL-1β significantly influences the expression of CC and CXC chemokine transcripts in FLSs, mirroring findings in chondrocytes, where human adult chondrocytes exhibit increased expression of CC and CXC chemokines [5]. Our finding that TGF-β1 effectively mitigates the inflammatory responses induced by IL-1β, potentially through suppression of transcription factor C/EBPβ, is novel. It highlights the potential of TGF-β1 as a therapeutic target for OA-related inflammatory conditions. These findings warrant further mechanistic studies to understand the inflammatory dynamics of FLSs in inflammatory arthritis.
2026-03-15 | GSE293257 | GEO
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:CD4+ T cells that selectively produce interleukin (IL)-17, are critical for host defense and autoimmunity. Crucial for T helper17 (Th17) cells in vivo, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-β1 have been argued to be the factors responsible for initiating specification. Herein, we show that Th17 differentiation occurs in the absence of TGF-β signaling. Neither IL-6 nor IL-23 alone efficiently generated Th17 cells; however, these cytokines in combination with IL-1β effectively induced IL-17 production in naïve precursors, independently of TGF-β. Epigenetic modification of the Il17a/Il17f and Rorc promoters proceeded without TGF-β1, allowing the generation of cells that co-expressed Rorγt and T-bet. T-bet+Rorγt+ Th17 cells are generated in vivo during experimental allergic encephalomyelitis (EAE), and adoptively transferred Th17 cells generated with IL-23 in the absence of TGF-β1 were more pathogenic in this experimental disease. These data suggest a new model for Th17 differentiation. Consistent with genetic data linking the IL23R with autoimmunity, our findings re-emphasize the role of IL-23 and therefore have important implications for the development of new therapies.
2010-08-31 | GSE23681 | GEO