FoxO1 inhibition by apelin/APJ signaling in endothelial cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE67390 | GEO | 2017/10/02
SECONDARY ACCESSION(S): PRJNA279797
REPOSITORIES: GEO
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Project description:Evaluation of gene transcripts that are downstream of apelin/APJ signaling in HUVECs
2013-05-11 | GSE46825 | GEO
Project description:Evaluation of gene transcripts that are downstream of apelin/APJ signaling in HUVECs Duplicates per group, subjected to: 1) control siRNA, 2) MEF2A and MEF2C siRNA, 3) G alpha 13 siRNA, and 4) apelin and APJ siRNA
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Project description:Evaluation of microRNAs that are downstream of apelin/APJ signaling in the pulmonary artery endothelial cells. Triplicates per group, subjected to: 1) control siRNA, 2) apelin siRNA, 3) APJ siRNA, 4) apelin + APJ siRNA
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Project description:Molecular pathways regulating the development of arterial and venous endothelial cells (ECs) are now well-established, but control of parallel arterial-venous (A-V) alignment is unclear. We report that arterial-venous alignment in the skin is determined by apelin receptor (APJ) expression in venous ECs. We used microarrays to detail the global programme of gene expression in endothelial cells that has relationship with the deficient of APJ. Endothelial cells were marked and isolated by Fluorescence-activated cell sorting in Trizol.
2016-07-03 | E-GEOD-66073 | biostudies-arrayexpress
Project description:Molecular pathways regulating the development of arterial and venous endothelial cells (ECs) are now well-established, but control of parallel arterial-venous (A-V) alignment is unclear. We report that arterial-venous alignment in the skin is determined by apelin receptor (APJ) expression in venous ECs.
2016-01-01 | GSE66073 | GEO
Project description:Brain arteriovenous malformations (bAVM) are characterized by enlarged blood vessels, which direct blood through arteriovenous AV shunts, bypassing the artery-capillary-vein network and disrupting blood flow. Clinically, bAVM treatments are invasive and not routinely applicable. There is critical need to understand mechanisms of bAVM pathologies and develop pharmacological therapies. We used an in vivo mouse model of Rbpj-mediated bAVM, which develops pathologies in the early postnatal period and an siRNA in vitro system to knockdown RBPJ in human brain microvascular endothelial cells (ECs). To understand molecular events regulated by endothelial Rbpj, we conducted RNA-Seq and ChIP-Seq analyses from isolated brain ECs. Rbpj-deficient (mutant) brain ECs acquired abnormally rounded shape (with no change to cell area), altered basement membrane dynamics, and increased EC density along AV shunts, compared to controls, suggesting impaired remodeling of neonatal brain vasculature. Consistent with impaired EC dynamics, we found increased Cdc42 activity in isolated mutant ECs, suggesting that Rbpj regulates small GTPase-mediated cellular functions in brain ECs. siRNA treated, RBPJ-deficient human brain ECs displayed increased Cdc42 activity, disrupted cell polarity and focal adhesion properties, and impaired migration in vitro. RNA-Seq analysis from isolated brain ECs identified differentially expressed genes in mutants, including Apelin, which encodes a ligand for G protein-coupled receptor signaling known to influence small GTPase activity. ChIP-Seq analysis revealed chromatin loci occupied by Rbpj in brain ECs that corresponded to G-protein and Apelin signaling molecules. In vivo administration of a competitive peptide antagonist against the Apelin receptor (Aplnr/Apj) attenuated Cdc42 activity and restored EC morphology and AV connection diameter in Rbpj-mutant brain vessels. Conclusions: Our data suggest that endothelial Rbpj promotes rearrangement of brain ECs during cerebrovascular remodeling, through Apelin/Apj-mediated small GTPase activity, and prevents bAVM. By inhibiting Apelin/Apj signaling in vivo, we demonstrated pharmacological prevention of Rbpj mediated bAVM.
2023-02-01 | GSE223532 | GEO
Project description:Brain arteriovenous malformations (bAVM) are characterized by enlarged blood vessels, which direct blood through arteriovenous AV shunts, bypassing the artery-capillary-vein network and disrupting blood flow. Clinically, bAVM treatments are invasive and not routinely applicable. There is critical need to understand mechanisms of bAVM pathologies and develop pharmacological therapies. We used an in vivo mouse model of Rbpj-mediated bAVM, which develops pathologies in the early postnatal period and an siRNA in vitro system to knockdown RBPJ in human brain microvascular endothelial cells (ECs). To understand molecular events regulated by endothelial Rbpj, we conducted RNA-Seq and ChIP-Seq analyses from isolated brain ECs. Rbpj-deficient (mutant) brain ECs acquired abnormally rounded shape (with no change to cell area), altered basement membrane dynamics, and increased EC density along AV shunts, compared to controls, suggesting impaired remodeling of neonatal brain vasculature. Consistent with impaired EC dynamics, we found increased Cdc42 activity in isolated mutant ECs, suggesting that Rbpj regulates small GTPase-mediated cellular functions in brain ECs. siRNA treated, RBPJ-deficient human brain ECs displayed increased Cdc42 activity, disrupted cell polarity and focal adhesion properties, and impaired migration in vitro. RNA-Seq analysis from isolated brain ECs identified differentially expressed genes in mutants, including Apelin, which encodes a ligand for G protein-coupled receptor signaling known to influence small GTPase activity. ChIP-Seq analysis revealed chromatin loci occupied by Rbpj in brain ECs that corresponded to G-protein and Apelin signaling molecules. In vivo administration of a competitive peptide antagonist against the Apelin receptor (Aplnr/Apj) attenuated Cdc42 activity and restored EC morphology and AV connection diameter in Rbpj-mutant brain vessels. Conclusions: Our data suggest that endothelial Rbpj promotes rearrangement of brain ECs during cerebrovascular remodeling, through Apelin/Apj-mediated small GTPase activity, and prevents bAVM. By inhibiting Apelin/Apj signaling in vivo, we demonstrated pharmacological prevention of Rbpj mediated bAVM.
2023-02-01 | GSE223531 | GEO
Project description:Transcriptome profiling of human umbilical vein endothelial cells (HUVECs) overexpressing constitutively nuclear FOXO1 to identify FOXO1 target genes.
2021-01-05 | GSE128634 | GEO
Project description:First, transcriptome analysis of purified CD31+ endothelial cells (ECs) from VEGF-treated sprouting embryoid bodies showed angiogenesis as the top affected category when Apelin is not present. In addition, loss of Apelin resulted in the modulation of pathways in ECs related to vasculogenesis, cell adhesion and response to hypoxia. Ingenuity Pathway Analysis (IPA) further identified VEGFR pathway as the main upstream regulator affected in endothelial cells, closely followed by the TGFβ1 and TNF pathways, all reduced in the absence of Apelin. The most inhibited genes from the VEGFR pathway in the absence of Apelin are angiogenesis-related genes. Second, transcriptome analysis of CD31+/CD105+ ECs sorted from Apelin wild-type and Apln-depleted tumors found a significant decrease in processes associated with endothelial cell proliferation and angiogenesis in ECs sorted out of Apelin-depleted tumors using IPA. Further, IPA predicted a decrease in the adhesion of granulocytes and upstream regulator analysis showed that proteins of the TGF-superfamily, Inhibin-βA and TGF-β1, as well as C/EBP-alpha, β-Catenin, ErbB2 and EGFR are predicted to be inhibited upstream regulators in ECs isolated from Apelin-depleted tumors.
2019-05-27 | GSE100293 | GEO