Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Endothelial to Mesenchymal Transition compromises vascular integrity to induce hypoxia and Myc mediated metabolic reprogramming of tubular epithelial cells in kidney fibrosis

ABSTRACT: The aim of this study was to identify the functional impact of Endothelial-to-Mesenchymal Transition (EndMT) in kidney fibrosis. For this purpose EndMT has been conditionally deleted in endothelial cells by the genetic deletion of Twist and Snail in the endothelial cells, using the tamoxifen inducible Cdh5-ERT2 Cre model. Twist EndMT–cKO and Snail EndMT–cKO mice, together with WT mice, were challanged with the unilateral ureteral obstruction model (UUO) to induce kidney fibrosis. Mice were euthanized 10 days after surgery. In addition, since we found that EndMT-induced vascular damage and hypoxia induces Myc upregulation in tubular epithelial cells (TECs), we deleted Myc in TECs (using the GGT-Cre model). Myc GGT–cKO mice were also challenged with the UUO model and euthanized 10 days after surgery.

ORGANISM(S): Mus musculus

PROVIDER: GSE144701 | GEO | 2020/06/09

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Genome-wide analysis of gene expression in normal and fibrotic mouse kidneys with and without Twist1 or with and without Snai1(Snail) expression in proximal tubular epithelial cells

Project description:In this study mice were engineered to specifically delete Twist1 or Snail expression in proximal tubular epithelial cells of the kidney (ggt-cre+;Twist flox/flox and ggt-cre+;Snail flox/flox ). These mice and control mice (ggtcre-;Twist flox/flox: these express Twist1, and ggtcre-;Snail flox/flox:these express Snail) were subjected to unilaterial ureteric obstruction. This experiment allows for the collection and analysis of expression in contralateral healthy (HK) kidney adn obstructed disease (DK) kidney. Total RNA was isolated from the contralateral healthy (HK) and obstructed disease (DK) kidneys of 3 mice with ggt-cre-;Twist flox/flox genotype (Wildtype like) and 4 mice with ggt-cre+;Twist flox/flox genotype (loss of Twist1 in proximal tubular epithelial cells), 3 mice with ggt-cre-;Snail flox/flox genotype (Wildtype like) and 3 mice with ggt-cre+;Snail flox/flox genotype (loss of Snail in proximal tubular epithelial cells). Total RNA was also isolated from kidneys of completely healthy mice: 3 mice ggt-cre-;WT, 3 mice ggt-cre+;WT, 3 mice ggt-cre+;Twist flox/flox and 3 ggt-cre+;Snail flox/flox

2015-08-03 | E-GEOD-60685 | biostudies-arrayexpress

Genome-wide analysis of gene expression in normal and fibrotic mouse kidneys with and without Twist1 or with and without Snai1(Snail) expression in proximal tubular epithelial cells

2015-08-03 | GSE60685 | GEO

Endothelial Cells from different anatomical origin have distinct responses during Snail/TGF-β2-mediated Endothelial-Mesenchymal Transition

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

Snail and Twist expression in HMLE and MCF10A cells

Project description:Snail and Twist are two EMT inducer, expression of Snail or Twist will induce EMT in HMLE and MCF10A cells. By introducing Snail or Twist in HMLE and MCF10A cells, which lack the expression of these two proteins, will identify the genes are induced during EMT. We used microarray analysis to compare the gene expression profiles between the mammamry epithleial cells and the cells undergone EMT.

2020-01-10 | GSE143349 | GEO

In vivo transcriptional activation using CRISPR-Cas9 in Drosophila

Project description:Identifying putative transcription factor target genes by combining CRISPR/Cas9-based transcriptional activation with RNAseq in Drosophila S2R+ cells. This study focuses on the transcription factors Twist and Snail, singly and together. RNA from Drosophila cells following CRISPR/Cas9-based activation of Twist, Snail, or Twist and Snail together, compared with non-targeting sgRNA. Two biological replicates for each experiment

2015-08-10 | E-GEOD-71430 | biostudies-arrayexpress

Genome-wide analysis of gene expression in mouse pancreas tumors

Project description:Genetically engineered mice developed spontaneous pancreas cancer (Pdx-Cre;LSL-KRASG12D;P53Mut). Mice were also engineered to develop similar spontaneous pancreas cancer without Twist or Snail (conditional gene knockout). The pancreas tumors were harvested and analysed for gene expression profiles comparisons. Total RNA was isolated from the pancreas tumors of 2 mice with wild-type Twist and Snail, from 2 mice without Twist expression in the pancreas, and from 2 mice without Snail expression in the pancreas.

2015-11-20 | E-GEOD-66981 | biostudies-arrayexpress

ChIP-chip mapping of twist, dorsal, snail, weckle in Drosophila embryos

Project description:We performed ChIP-chip analysis using sheared chromatin isolated from Drosophila embryos of 1-3 hours in age. Keywords: high-resolution tiling array, drosophila, twist, dorsal, snail, weckle ChIP-chip of twist, dorsal, snail, and weckle

2011-02-28 | E-GEOD-26285 | biostudies-arrayexpress

Monocytes Release Endogenous Retroviral Protein in Exosomes Causing a Mesenchymal, Proinflammatory Endothelium and Pulmonary Hypertension

Project description:Human endogenous retroviral (HERV) proteins are induced by exogenous viruses or other factors that derepress HERV transcription and translation. Previously we showed that HERV-K envelope and deoxyuridine triphosphate nucleotidohydrolase (dUTPase) proteins are increased in monocytes and macrophages from patients with pulmonary arterial hypertension (PAH). Recombinant HERV-K dUTPase upregulates IL6 in pulmonary arterial endothelial cells (PAECs) and induces pulmonary hypertension in rats. However, it was not known how HERV-K dUTPase released from monocytes engages PAECs to upregulate IL6 or induces other PAH features of PAEC dysfunction. Here we report that HERV-K dUTPase recruits TLR4-myeloid differentiation primary response-88 to increase IL6 and SNAIL, the endothelial-mesenchymal transition (EndMT) transcription factor; HERV-K dUTPase interaction with melanoma cell adhesion molecule (MCAM) upregulates VCAM1. p38 and NF-kB are required to increase expression of all three genes, but in addition, pJNK-pSMAD3 is necessary for SNAIL upregulation, STAT1 for IL6, and pERK1/2-activating transcription factor-2 for VCAM1. Packaging of HERV-K dUTPase in monocyte-derived extracellular vesicles (EVs) induces SNAIL and subsequent EndMT in PAECs, IL6 and VCAM1. Mice infused with EVs from monocytes transfected with HERV-K dUTPase develop pulmonary hypertension. Thus, retroviral proteins delivered in EVs can overtake PAEC signaling and transcriptional machinery to induce dysfunction associated with PAH.

2020-08-24 | MSV000086005 | MassIVE

LARP7 suppresses endothelial-to-mesenchymal transition by coupling with TRIM28

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

The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition [HTS]

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data