Transcriptome changes during Endothelial to Mesenchymal Transition (EndMT) using a TGF-b2 and IL-1b in vitro model of EndMT in HUVEC and HPAEC
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE118446 | GEO | 2020/12/31
REPOSITORIES: GEO
Similar Datasets
Project description:Endothelial-to-mesenchymal transition (EndMT) is a dynamic biological process involved in pathological vascular remodeling. However, the molecular mechanisms that govern this transition remain largely unknown. To study EndMT in vitro, human umbilical vein endothelial cells (HUVEC) were treated with transforming growth factor-β2 and interleukin-1β, leading to a decrease of endothelial markers as well as an increase of mesenchymal markers and EndMT regulators after 7 days. Single-cell RNA-seq was carried out to study the dynamics of the transition.
2021-04-06 | GSE159843 | GEO
Project description:Endothelial-to-mesenchymal transition (EndMT) is a dynamic transformation process that has a functional impact upon pathological vascular remodelling. The molecular mechanisms that govern EndMT remain largely unknown. By induction of EndMT in human primary endothelial cells (EC), using a combination of transforming growth factor-β2 (TGF-b2) and interleukin-1b (IL-1β), we identified the dramatic loss of the lncRNA MIR503HG, as a common signature across multiple primary EC types. Targeted depletion of MIR503HG spontaneously induced EndMT. Overexpression of MIR503HG repressed EndMT despite TGF-β2 and IL-1β co-stimulation. RNA-seq was carried out to identify the changes in gene expression induced by MIR503HG overexpression. We showed that over 25% of the EndMT-transcriptome signature was inhibited upon MIR503HG overexpression. Crucially, phenotypic changes induced by MIR503HG were independent of the functional regulation of miR-503 and miR-424, both harbored within the MIR503HG locus. Collectively, we identify the lncRNA MIR503HG as an essential regulator of EndMT.
2020-12-31 | GSE118815 | GEO
Project description:Endothelial-mesenchymal transition (EndMT) is a complex process, in which differentiated endothelial cells undergo phenotypic transition to mesenchymal cells. Given the diversity of the vascular system in architecture, structure, and embryonic origins, it is not clear if endothelial cells lining different vessels are able to undergo EndMT. Therefore, the aim of this study was to evaluate the molecular and functional changes that occur in different types of endothelial cells after induction of EndMT through overexpression of Snail and TGF-β2. Different types of endothelial cells (human umbilical vein, heart, and lung) have distinct response when induced to undergo EndMT. Coronary artery endothelial cells (HCAEC) induced with combined Snail overexpression plus TGF-β2 treatment promotes a decrease of endothelial markers, an increase of mesenchymal markers and migration. The mechanism that HCAEC undergoing EndMT may be mediated through Notch and non-canonical Wnt signaling pathways. These results provide the foundation for understanding the roles of specific signaling pathways in mediating EndMT in endothelial cells from different anatomical origin.
2017-04-22 | GSE96089 | GEO
Project description:Transcriptome changes during Endothelial to Mesenchymal Transition (EndMT) using a TGF-b2 and IL-1b in vitro model of EndMT in HUVEC and HPAEC
| PRJNA485688 | ENA
Project description:Bulk RNA-Seq revealed that activation of the endogenous CD45 promoter induced expression of several genes implicated in EndMT. CD45-positive endothelial cells showed significantly increased migration, a hallmark of EndMT, increased collagen gel contraction, a hallmark of mesenchymal cells, and decreased cell-cell barrier integrity, indicating reduced endothelial function.
2023-05-03 | GSE207837 | GEO
Project description:Endothelial cells play an important role in maintenance of the vascular system and the repair after injury. Under pro-inflammatory conditions, endothelial cells can acquire a mesenchymal phenotype by a process named endothelial-to-mesenchymal transition (EndMT), which affects the functional properties of endothelial cells. Here, we investigated the epigenetic control of EndMT. We show that the histone demethylase JMJD2B is induced by EndMT promoting pro-inflammatory and hypoxic conditions. Silencing of JMJD2B reduced TGF-β2-induced expression of mesenchymal genes and prevented the alterations in endothelial morphology and impaired endothelial barrier function. Endothelial-specific deletion of JMJD2B in vivo confirmed a reduction of EndMT after myocardial infarction. EndMT did not affect global H3K9me3 levels but induced a site-specific reduction of repressive H3K9me3 marks at promoters of mesenchymal genes, such as Calponin (CNN1), and genes involved in TGF-β signaling, such as AKT Serine/Threonine Kinase 3 (AKT3) and sulfatase 1 (SULF1). Silencing of JMJD2B prevented the EndMT-induced reduction of H3K9me3 marks at these promotors and further repressed these EndMT-related genes. Our study reveals that endothelial identity and function is critically controlled by the histone demethylase JMJD2B, which is induced by EndMT-promoting pro-inflammatory and hypoxic conditions and support the acquirement of a mesenchymal phenotype.
2020-01-08 | GSE143148 | GEO
Project description:Endothelial cells play an important role in maintenance of the vascular system and the repair after injury. Under pro-inflammatory conditions, endothelial cells can acquire a mesenchymal phenotype by a process named endothelial-to-mesenchymal transition (EndMT), which affects the functional properties of endothelial cells. Here, we investigated the epigenetic control of EndMT. We show that the histone demethylase JMJD2B is induced by EndMT promoting pro-inflammatory and hypoxic conditions. Silencing of JMJD2B reduced TGF-β2-induced expression of mesenchymal genes and prevented the alterations in endothelial morphology and impaired endothelial barrier function. Endothelial-specific deletion of JMJD2B in vivo confirmed a reduction of EndMT after myocardial infarction. EndMT did not affect global H3K9me3 levels but induced a site-specific reduction of repressive H3K9me3 marks at promoters of mesenchymal genes, such as Calponin (CNN1), and genes involved in TGF-β signaling, such as AKT Serine/Threonine Kinase 3 (AKT3) and sulfatase 1 (SULF1). Silencing of JMJD2B prevented the EndMT-induced reduction of H3K9me3 marks at these promotors and further repressed these EndMT-related genes. Our study reveals that endothelial identity and function is critically controlled by the histone demethylase JMJD2B, which is induced by EndMT-promoting pro-inflammatory and hypoxic conditions and support the acquirement of a mesenchymal phenotype.
2020-01-08 | GSE143150 | GEO
Project description:Rational: We previously reported evidence of endothelial to mesenchymal transition (EndMT) and fibrosis in mitral valve (MV) leaflets at two to six months post-myocardial infarction (MI) in sheep. The onset of these changes and the mechanism of their instigation are not known. Early modulation of EndMT and fibrosis in MV leaflets may limit the development of ischemic mitral regurgitation (IMR) and heart failure. H Objective: To test the hypothesis that circulating molecules present in plasma within days after MI incite EndMT and fibrotic processes in MV leaflets. Method and Results: Ovine MVs harvested 8-10 days after inferior MI (IMI) showed an increase in MV thickness by histology and onset of EndMT, shown by increased CD31/α-smooth muscle actin (α-SMA)+ cells in post-MI MV leaflets (10.5±6.9%) versus sham (2.6±4%). In vitro, post-MI plasma induced EndMT and pro-fibrotic markers and enhanced migration of primary mitral valve endothelial cells (VECs). In contrast, sham plasma did not, despite the presence of TGFβ2 at levels known to induce EndMT in VECs (2 ng/ml). Analysis of sham versus post-MI plasma using a cytokine array revealed a significant drop in the Wnt signaling antagonist secreted frizzled-related protein 3 (sFRP3) in post-MI plasma compared to sham plasma, which was confirmed by ELISA. Addition of recombinant sFRP3 to post-MI plasma reversed its EndMT-inducing effect on mitral VECs, measured by restored VE-cadherin, reduced α-SMA, and reduced TGFβ1-3 expression. Extracellular signal related kinase 1/2 and SMAD2/3 phosphorylation were increased in mitral VEC by post-MI plasma, and both were blocked by supplementing the post-MI plasma with sFRP3. RNA-seq analysis of mitral VECs exposed to post-MI versus sham plasma for 24 hours showed upregulated forkhead box M1 (FOXM1), a transcription factor previously shown to drive fibrosis. FOXM1 was co-localized with CD31 in MV leaflets obtained from sheep at 8-10 days post-MI, which suggests FOXM1 may be linked to EndMT initiation. Blocking FOXM1 with Siomycin A (Sio A) reduced EndMT and pro-fibrotic transcripts in post-MI plasma treated mitral VECs. Finally, post-MI plasma-induced and TGFβ-induced FOXM1 was downregulated by sFRP3. Conclusions: Reduced sFRP3 in post-MI plasma appears to facilitate the onset of TGFβ-driven EndMT and fibrosis in mitral VECs by increasing the transcription factor FOXM1. Restoring sFRP3 levels and/or inhibiting FOXM1 may provide new strategies to minimize maladaptive changes that occur in the MV due to MI.
2022-01-15 | GSE182696 | GEO
Project description:LARP7 plays a pivotal role in regulating endothelial-to-mesenchymal transition(EndMT) and EndMT-associated heart valve formation. LARP7 directly interactes with TRIM28 and cooperatively represses SLUG transcription, which thereby suppresses EndMT of endothelial cells. More importantly, inducible knockout of LARP7 or TRIM28 in the endocardium promotes EndMT in vivo and leads to the valvular hyperplasia.
2023-09-22 | GSE165400 | GEO
Project description:Lipodystrophy syndromes (LD) are characterized by loss of adipose tissue, metabolic complications such as dyslipidemia, insulin resistance and fatty liver disease, as well as accelerated atherosclerosis. As a result of adipose tissue deficiency, the systemic concentration of the adipokine leptin is reduced. A current promising therapeutic option for patients with LD is treatment with recombinant leptin (metreleptin) resulting in reduced risk of mortality. Here, we investigate the effects of leptin on endothelial-to-mesenchymal transition (EndMT), which impairs the functional properties of endothelial cells and promotes atherogenesis in LD. Leptin treatment reduced inflammation, TGF-β2-induced expression of mesenchymal genes and prevented impairment of endothelial barrier function. Treatment of lipodystrophic and atherosclerosis prone animals (Ldlr-/-; aP2-nSrebp1c-Tg) with leptin reduced macrophage accumulation in atherosclerotic lesions, vascular plaque protrusion and the number of endothelial cells with mesenchymal gene expression, confirming a reduction in EndMT in LD after leptin treatment. Treatment with leptin inhibited LD-mediated induction of the pro-atherosclerotic cytokine growth/differentiation factor 15 (GDF15). Inhibition of GDF15 reduced EndMT induction triggered by plasma from LD patients. Our study reveals that in addition to the effects on adipose tissue function, leptin treatment exerts beneficial effects protecting endothelial function and identity in LD by reducing GDF15.
2022-09-20 | GSE213438 | GEO