Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

GPR174 Knockdown Enhances Blood Flow Recovery in Hindlimb Ischemia Mice Model by Upregulating AREG Expression

ABSTRACT: Regulatory T cells (Tregs) are critically involved in neovascularization, an important compensatory mechanism in peripheral artery disease (PAD). The contribution of G protein coupled receptor 174 (GPR174), which is a regulator of Treg function and development, in neovascularization remains elusive. Here, we reveal that genetic deletion of GPR174 in Tregs potentiated blood flow recovery in mice after hindlimb ischemia (HLI). GPR174 deficiency upregulates amphiregulin (AREG) expression in Tregs, thereby enhancing endothelial cell functions and reducing pro-inflammatory macrophage polarization and endothelial cell apoptosis. Mechanically, GPR174 regulates AREG expression by inhibiting the nuclear accumulation of early growth response protein 1 (EGR1) via Gαs/cAMP/PKA signal pathway activation. Collectively, these findings demonstrate that GPR174 negatively regulates angiogenesis and vascular remodeling in response to ischemic injury and that GPR174 may be a potential molecular target for therapeutic interventions of ischemic vascular diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE214684 | GEO | 2022/10/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Endothelial CXCL12 regulates neovascularization during tissue repair and tumor progression

Project description:Tissue repair and tumor progression are linked by their reliance on the response to ischemia. Coordinated interplay between resident and circulating cells, governed by a myriad of factors, is critical for new blood vessel formation and tissue survival in both. The vascular endothelium exhibits paracrine activity and provides an interface for the recruitment of circulating cells, which in turn influence the neovascularization and extra-vascular tissue growth. CXC chemokine ligand 12 (CXCL12; stromal cell-derived factor 1 [SDF-1]) has been implicated in tumor biology and neovascularization, but its specific role and mechanism of action remain poorly understood. We have previously demonstrated that CXCL12 expression is hypoxia responsive and occurs in vascular endothelium. Here we use a conditional CXCL12 knockout mouse to show that endothelial-specific deletion of CXCL12 (eKO) reduces the survival of ischemic tissue, which alters both tissue repair and tumor progression. The loss of vascular endothelial CXCL12 disrupts endothelial – fibroblast crosstalk necessary for stromal growth and vascularization. Using single-cell gene expression analysis in combination with a parabiosis model, eKO is found to impair the recruitment of a specific population of non-inflammatory circulating cells defined by genes regulating cell survival and neovascularization. These findings indicate an essential role of endothelial CXCL12 expression during the adult neovascular response in tissue injury and tumor progression, paving the way for future therapeutic interventions.

2020-03-07 | GSE146529 | GEO

A KLF2-BMPER-Smad1/5 checkpoint regulates high fluid shear stress-mediated artery remodeling

Project description:Vascular remodeling to match arterial diameter to tissue metabolic requirements commonly fails in ischemic disease. Endothelial cells (EC) sense fluid shear stress (FSS) from blood flow to maintain FSS within a narrow range in healthy vessels. Higher FSS induces vessel outward remodeling to return FSS to physiological levels, but mechanisms are poorly understood. We previously reported that Smad1/5 is maximally activated at physiological FSS and suppressed at higher flow. The Smad1/5 pathway opposes activation of Akt, suggesting that inhibiting Smad1/5 may be required for outward remodeling. Here, we report that suppression of Smad1/5 at high FSS is mediated by elevated KLF2, which induces the BMP pathway inhibitor BMPER, which suppresses Smad1/5 and de-inhibits Akt. In a mouse arteriovenous fistula (AVF) model, high FSS induces arterial outward remodeling coincident with elevated BMPER expression and Smad1/5 inactivation. Endothelial BMPER deletion impaired blood flow recovery and vascular remodeling in the AVF and a hindlimb ischemia (HLI) model, with the latter reversed by BMP9/10 blocking antibodies (bAbs). In both STZ-induced type 1 and HFD-induced type 2 diabetic mice that show poor recovery from HLI, BMP9/10 bAbs improved outcomes. Thus, suppression of Smad1/5 is required for high FSS-mediated outward remodeling and is a potential therapeutic approach for ischemic disease.

2024-05-24 | GSE267813 | GEO

Genome-wide analysis gene expression of MCF10A cells growing in the presence of EGF or AREG or without EGF or AREG for 24 hrs

Project description:Results of growing MCF10A cells continuously in serum free media supplemented with EGF (MCF10A) or AREG (MCF10A+AREG) followed by 24 hours of ligand withdrawl and measuring gene expression provides information as to what genes are regulated by AREG and EGF in a normal mammary epithelial cell model MCF10A cells continuously in serum free media supplemented with 10ng/ml of EGF (MCF10A) or 20ng/ml of AREG (MCF10A+AREG) followed by 24 hours of ligand withdrawl. Total RNA was collected and genome-wide analysis of expression was performed on RNA from each cell line.

2010-12-23 | E-GEOD-26264 | biostudies-arrayexpress

Genome-wide analysis gene expression of MCF10A cells growing in the presence of EGF or AREG or without EGF or AREG for 24 hrs

2010-12-23 | GSE26264 | GEO

HDC/histamine signaling axis drives macrophage reprogramming to promote angiogenesis in the hindlimb ischemia mice

Project description:Histamine is catalyzed by histidine decarboxylase (HDC), which plays important roles in many physiological and pathological processes, but its role in angiogenesis has not been thoroughly clarified. Here we report that HDC is highly expressed in Ly6C+macrophages, rather than in endothelial cells using Hdc-GFP transgenic mice with hindlimb ischemia (HLI) mouse model. Given the whole-process promoting effect of macrophages on angiogenesis, a cluster of HDC+CXCR2+ macrophages have been identified by single-cell sequencing technology in ischemic tissue. The inactivation of HDC leads to a lack of histamine and pro-angiogenic factor production in macrophages, inducing a harsh inflammatory microenvironment that is not conducive to the interaction between macrophages and endothelial cells. Moreover, HA-DA@histamine hydrogel has been designed and demonstrated to safely treat ischemic injury by modulating inflammation and angiogenesis. These data highlight the critical roles of HDC/histamine signaling in macrophage differentiation, angiogenesis, and muscle regeneration in the early stage of HLI.

2024-08-02 | GSE273730 | GEO

GPR174 knockdown enhances blood flow recovery in hindlimb ischemia mice model by upregulating AREG expression.

Project description:Regulatory T cells (Tregs) are critically involved in neovascularization, an important compensatory mechanism in peripheral artery disease. The contribution of G protein coupled receptor 174 (GPR174), which is a regulator of Treg function and development, in neovascularization remains elusive. Here, we show that genetic deletion of GPR174 in Tregs potentiated blood flow recovery in mice after hindlimb ischemia. GPR174 deficiency upregulates amphiregulin (AREG) expression in Tregs, thereby enhancing endothelial cell functions and reducing pro-inflammatory macrophage polarization and endothelial cell apoptosis. Mechanically, GPR174 regulates AREG expression by inhibiting the nuclear accumulation of early growth response protein 1 (EGR1) via Gαs/cAMP/PKA signal pathway activation. Collectively, these findings demonstrate that GPR174 negatively regulates angiogenesis and vascular remodeling in response to ischemic injury and that GPR174 may be a potential molecular target for therapeutic interventions of ischemic vascular diseases.

| S-EPMC9727025 | biostudies-literature

Genome-wide analysis gene expression in SUM-149 cells expressing AREG shRNA

Project description:Results of knocking-down AREG expression in SUM-149 cells by lenitviral infection of shRNA vectors and measuring gene expression provides information as to what genes are regulated by AERG in inflammatory breast cancer cells. SUM-149 cells were infected with a single AREG shRNA virus (sh4) or three AREG shRNA viruses (shPld) and the non-silencing vector (shNS). Total RNA was collected and genome-wide analysis of expression was performed on RNA from each cell line.

2010-12-15 | E-GEOD-26079 | biostudies-arrayexpress

GPR174 Knockdown Enhances Blood Flow Recovery in Hindlimb Ischemia Mice Model by Upregulating AREG Expression

Project description:GPR174 Knockdown Enhances Blood Flow Recovery in Hindlimb Ischemia Mice Model by Upregulating AREG Expression

| PRJNA886679 | ENA

Vascular Permeability and Apoptosis are Separable Processes in Retinal Ischemia-Reperfusion Injury

Project description:Effects of Ischemic Preconditioning, Bevacizumab and Etanercept Ischemia and reperfusion injury provides an acute model of ischemic retinopathy that includes neurodegeneration and VEGF-dependent vascular permeability and is amenable to rapid drug testing. The distinct effects of ischemic preconditioning and bevacizumab demonstrate that the apoptotic and vascular responses to ischemia may be separated and that VEGF expression is not neuroprotective following ischemic-reperfusion. Using transient ischemia followed by reperfusion (IR) to model ischemic retinal disease, this study compares the effects of ischemic preconditioning (IPC) and therapies targeting vascular endothelial growth factor (VEGF) and tumor necrosis factor α (TNFα) on retinal apoptosis, vascular permeability and mRNA biomarker expression. Only the Ischemic Preconditioning (not Bevacizumab and Etanercept treated samples) were hybridized to arrays. Study contains 6 replicates of control and 6 IP treated retinal samples.

2010-05-31 | E-GEOD-20521 | biostudies-arrayexpress

Changes in bone marrow resident monocyte gene expression upon induction of ischemia

Project description:There is considerable interest in the potential of cell-based approaches to mediate therapeutic angiogenesis for acute and chronic vascular syndromes. Using a mouse model of HLI, we showed previously that adoptive transfer of a small number of donor monocytes enhanced revascularization significantly. Herein, we provide data suggesting that the BM resident monocytes sense systemic signals that influence their future functional capacity. Specifically, following induction of distant ischemia, the angiogenic capacity of BM resident monocytes is reduced markedly. We provide evidence that G-CSF and IL-6 represent such conditioning signals. Systemic levels of G-CSF and IL-6 are increased significantly following induction of HLI. Accordingly, BM resident monocytes from ischemic mice exhibited increased pSTAT3 and STAT3 target gene expression. Finally, G-CSFR(-/-) and IL-6(-/-) mice were resistant to the deleterious effects of ischemic conditioning on monocyte angiogenic potential. RNA expression profiling suggested that ischemia-conditioned monocytes in the BM up-regulate the well-described M2 polarization markers Chi3l4 and Lrg1. Consistent with this observation, M2-skewed monocytes from SHIP(-/-) mice also had impaired angiogenic capacity. Collectively, these data show that G-CSF and IL-6 provide signals that determine the angiogenic potential of BM resident monocytes. Bone marrow was harvested from CX3CR1+/GFP heterozygous mice and CX3CR1-GFP+ monocytes were sorted at baseline and at 24 hours post-induction of hindlimb ischemia by femoral artery ligation. Paired samples from three independent experiments were analyzed.

2010-04-26 | E-GEOD-21509 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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