Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA327078 | ENA |
REPOSITORIES: ENA
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Project description:The formation of new blood vessels is essential for normal development, tissue repair and tumor growth. Here we show that inhibition of the kinase p38α enhances angiogenesis in human and mouse colon tumors. Mesenchymal cells can contribute to tumor angiogenesis by regulating proliferation and migration of endothelial cells. We show that p38α negatively regulates an angiogenic program in mesenchymal stem/stromal cells (MSCs), multipotent progenitors found in perivascular locations. This program includes the acquisition of an endothelial phenotype by MSCs mediated by both TGF-β and JNK, and negatively regulated by p38α. Abrogation of p38α in mesenchymal cells increases tumorigenesis, which correlates with enhanced angiogenesis. Using genetic models, we show that p38α regulates the acquisition of an endothelial-like phenotype by mesenchymal cells in colon tumors and damage tissue. Taken together, our results indicate that p38α in mesenchymal cells restrains a TGF-β-induced angiogenesis program including their ability to transdifferentiate into endothelial cells.
2019-10-02 | GSE83810 | GEO
Project description:Analysis of primary bovine aortic endothelial cells treated for 24 hours with TGF-beta 1 5 ng/ml. TGF-beta 1 has been shown to induce endothelial-to-mesenchymal transition (EndoMT) and to be implicated in differentiation of endothelial cells into smooth muscle-like cells as occurred in vascular neointimal formation. Primary aortic endothelial cells seeded on 10 mm diameter plates were incubated with TGF-beta 1 (5 ng/ml) for 24 hours or left under basal conditions. Triplicates from three different cultures.
2013-04-10 | E-GEOD-42932 | biostudies-arrayexpress
Project description:Tumor microenvironment contains various components including cancer cells, tumor vessels, and cancer associated fibroblasts (CAFs), comprising of tumor-promoting myofibroblasts and tumor-suppressing fibroblasts. Multiple lines of evidence indicated that transforming growth factor-β (TGF-β) induces the formation of myofibroblasts and other types of mesenchymal (non-myofibroblastic) cells from endothelial cells. Recent reports showed that fibroblast growth factor 2 (FGF2) modulates TGF-β-induced mesenchymal transition of endothelial cells, but the molecular mechanisms regarding the signals that control the transcriptional networks during the formation of different groups of fibroblasts remain largely unclear. Here, we studied the roles of FGF2 during the regulation of TGF-β-induced mesenchymal transition of tumor endothelial cells (TECs). We demonstrated that auto/paracrine FGF signals in TECs inhibit TGF-β-induced endothelial-to-myofibroblast transition (End-MyoT), leading to suppressed formation of contractile myofibroblast cells, but on the other hand can also collaborate with TGF-β in promoting the formation of active fibroblastic cells which have migratory and proliferative properties. FGF2 modulated TGF-β-induced formation of myofibroblastic and non-myofibroblastic cells from TECs via transcriptional regulation of the array of various mesenchymal markers and growth factors. Furthermore, we observed that TECs treated with TGF-β were more competent in promoting in vivo tumor growth than TECs treated with TGF-β and FGF2. Mechanistically, we showed that Elk1 mediated this FGF2-induced inhibition of End-MyoT via inhibition of TGF-β-induced transcriptional activation of α-SMA promoter by myocardin-related transcription factor (MRTF)-A. Our data suggest that TGF-β and FGF2 oppose and cooperate with each other during the formation of myofibroblastic and non-myofibroblastic cells from TECs to determine the characteristics of the mesenchymal cells in tumor microenvironment. Identification of marker genes for TGF-β-induced endothelial-to-myofibroblast transition
2019-05-15 | GSE129048 | GEO
Project description:MicroRNA-31 regulates endothelial-to-mesenchymal transition and associated secretory phenotype induced by TGF-β.
2015-11-30 | GSE70207 | GEO
Project description:Analysis of primary bovine aortic endothelial cells treated for 24 hours with TGF-beta 1 5 ng/ml. TGF-beta 1 has been shown to induce endothelial-to-mesenchymal transition (EndoMT) and to be implicated in differentiation of endothelial cells into smooth muscle-like cells as occurred in vascular neointimal formation.
2013-04-10 | GSE42932 | GEO
Project description:TGF-beta plays multiple functions in a board range of cellular responses such as proliferation, differentiation, motility and survival by activating several cellular signaling pathways, including Smads and MAP kinases (Erk, JNK and p38). In particular, TGF-beta can activate pro- or anti-apoptotic signals depending on the target cells. We found that blockage of JNK activation sensitized mouse B lymphoma derived A20 cells to TGF-beta-induced apoptosis. These results suggest that TGF-beta activate JNK to inhibit the activation of death signal that is simultaneously activated by TGF-beta. We used microarrays to gain insight into the effects of JNK inhibition on gene expression in TGF-b-stimulated A20 cells and identified JNK-dependent TGF-beta inducible genes. Experiment Overall Design: The following six samples were prepared: untreated A20 cells (non-stimulated, DMSO): A20 cells cultured with SP600125 for 24 h (non-stimulated, SP600125): A20 cells stimulated with TGF-beta for 12 h (TGF-beta 12 h, DMSO) and 24 h (TGF-beta 24 h, DMSO): and A20 cells stimulated with TGF-beta in the presence of SP600125 for 12 h (TGF-beta 12 h, SP600125) and 24 h (TGF-beta 24 h, SP600125), respectively. Total RNA was prepared and hybridized to the Affymetrix Mouse Genome 430 2.0 array. Genes whose expression was increased by more than 2-fold at either 12 or 24 h after TGF-beta stimulation were identified as TGF-beta inducible genes. Amongst them, we identified genes whose induction levels were reduced by more than 75% by co-treatment with the JNK inhibitor SP600125.
2008-06-15 | E-GEOD-7503 | biostudies-arrayexpress
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:Endothelial to mesenchymal transition (EndoMT) plays a key role in heart development, but is also implicated in cardiovascular diseases in postnatal life. While the roles of TGF-β as inducer of EndoMT on the transcriptional level are well characterised, its post-transcriptional regulatory mechanisms remain largely unknown. Here, we identified global changes in the endothelial mRNA bound proteome upon TGF-β stimulation using RNA interactome capture. Characterisation of TGF-β regulated RNA binding proteins (RBPs) revealed heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) and Cold Shock Domain Containing E1 (Csde1) as key regulators of endothelial function and EndoMT. We profiled TGF-β driven changes in the RNA binding patterns of hnRNP H1 and Csde1 and found that they dynamically bind and regulate specific subsets of functionally connected RNAs related to mesenchymal activation upon TGF-β stimulation. Together, we show that RBPs play a key role in EndoMT and that the RBPs hnRNP H1 and Csde1 maintain endothelial cell function and counteract mesenchymal activation.
2023-10-01 | GSE216227 | GEO
Project description:Endothelial to mesenchymal transition (EndoMT) plays a key role in heart development, but is also implicated in cardiovascular diseases in postnatal life. While the roles of TGF-β as inducer of EndoMT on the transcriptional level are well characterised, its post-transcriptional regulatory mechanisms remain largely unknown. Here, we identified global changes in the endothelial mRNA bound proteome upon TGF-β stimulation using RNA interactome capture. Characterisation of TGF-β regulated RNA binding proteins (RBPs) revealed heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) and Cold Shock Domain Containing E1 (Csde1) as key regulators of endothelial function and EndoMT. We profiled TGF-β driven changes in the RNA binding patterns of hnRNP H1 and Csde1 and found that they dynamically bind and regulate specific subsets of functionally connected RNAs related to mesenchymal activation upon TGF-β stimulation. Together, we show that RBPs play a key role in EndoMT and that the RBPs hnRNP H1 and Csde1 maintain endothelial cell function and counteract mesenchymal activation.
2023-10-01 | GSE216226 | GEO
Project description:TGF-beta plays multiple functions in a board range of cellular responses such as proliferation, differentiation, motility and survival by activating several cellular signaling pathways, including Smads and MAP kinases (Erk, JNK and p38). In particular, TGF-beta can activate pro- or anti-apoptotic signals depending on the target cells. We found that blockage of JNK activation sensitized mouse B lymphoma derived A20 cells to TGF-beta-induced apoptosis. These results suggest that TGF-beta activate JNK to inhibit the activation of death signal that is simultaneously activated by TGF-beta. We used microarrays to gain insight into the effects of JNK inhibition on gene expression in TGF-b-stimulated A20 cells and identified JNK-dependent TGF-beta inducible genes. Keywords: time course
2007-08-01 | GSE7503 | GEO