M1 microglia disrupt the barrier function of retinal microvascular endothelial cells via ANGPT2/TIE2 axis
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ABSTRACT:
PROVIDER: PRJEB90177 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR15104168_1.fastq.gz | Fastqsanger.gz | |||
| ERR15104168_2.fastq.gz | Fastqsanger.gz | |||
| ERR15104169_1.fastq.gz | Fastqsanger.gz | |||
| ERR15104169_2.fastq.gz | Fastqsanger.gz | |||
| ERR15104170_1.fastq.gz | Fastqsanger.gz |
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Project description:Glomerular diseases are the leading cause of chronic kidney diseases with pathomechanisms largely unclear. It is known that ANGPT2 regulates endothelial cell homeostasis and function via TEK/TIE2 and its deregulation causes endothelial damage. We found that ANGPT2 is upregulated in glomerular diseases and wondered whether it has any effect on glomerular podocytes and mesangial cells given that they have no or low TEK expression. We treated podocytes and mesangial cells in culture with ANGPT2 and found no overt cellular changes. RNA-seq analysis showed that gene expression was altered in both podocytes and mesangial cells and that the regulated genes in the two cell types were fundamentally different. GO and KEGG analyses showed that the two groups of regulated genes were enriched in distinct processes and pathways. These results suggest that ANGPT2 exerts effects on both podocytes and mesangial cells and that increased ANGPT2 may be involved in glomerular injury by affecting podocytes and mesangial cells in addition to endothelial cells.
2022-01-10 | GSE185293 | GEO
Project description:Glomerular diseases are the leading cause of chronic kidney diseases with pathomechanisms largely unclear. It is known that ANGPT2 regulates endothelial cell homeostasis and function via TEK/TIE2 and its deregulation causes endothelial damage. We found that ANGPT2 is upregulated in glomerular diseases and wondered whether it has any effect on glomerular podocytes and mesangial cells given that they have no or low TEK expression. We treated podocytes and mesangial cells in culture with ANGPT2 and found no overt cellular changes. RNA-seq analysis showed that gene expression was altered in both podocytes and mesangial cells and that the regulated genes in the two cell types were fundamentally different. GO and KEGG analyses showed that the two groups of regulated genes were enriched in distinct processes and pathways. These results suggest that ANGPT2 exerts effects on both podocytes and mesangial cells and that increased ANGPT2 may be involved in glomerular injury by affecting podocytes and mesangial cells in addition to endothelial cells.
2022-01-10 | GSE185292 | GEO
Project description:Invasive nonfunctioning (NF) pituitary neuroendocrine tumors (PitNETs) are non-resectable neoplasms associated with frequent relapses and significant comorbidities. As the current therapies of NF-PitNETs often fail, new therapeutic targets are needed. The observation that circulating angiopoietin-2 (ANGPT2) is elevated in patients with NF-PitNET and correlates with tumor aggressiveness prompted us to investigate the ANGPT2/TIE2 axis in NF-PitNETs in the GH3 PitNET cell line, primary human NF-PitNET cells, xenografts in zebrafish and mice, and in MENX rats, the only autochthonous NF-PitNET model. We show that PitNET cells express a functional TIE2 receptor and secrete bioactive ANGPT2, which promotes, besides angiogenesis, tumor cell growth in an autocrine and paracrine fashion. ANGPT2 stimulation of TIE2 in tumor cells activates downstream cell proliferation signals, as previously demonstrated in endothelial cells (ECs). Tie2 gene deletion blunts PitNETs growth in xenograft models, and pharmacological inhibition of Angpt2/Tie2 signaling antagonizes PitNETs in primary cell cultures, tumor xenografts in mice, and in MENX rats. Thus, the ANGPT2/TIE2 axis provides an exploitable therapeutic target in NF-PitNETs and possibly in other tumors expressing ANGPT2/TIE2. The ability of tumor cells to coopt angiogenic signals classically viewed as EC-specific expands our view on the microenvironmental cues that are essential for tumor progression.
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Project description:The functional role of tumor cell-expressed Angpt2 still remains elusive. Here, we used mouse melanoma cells which have endgeneous Angpt2 expression and invesitgated the functional role of tumor cell-derived Angpt2. Total RNA from control and Angpt2 silenced mouse melanoma cells (RET) was isolated and was further utilized for microarray analysis using Affymetrix Mouse Gene 2.0 ST array.
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Project description:Diabetes is an incurable, long-term, chronic disease that can lead to a variety of complications, including angiopathy, peripheral neuropathy, kidney disease, erectile dysfunction (ED), and infections. The angiopoietin-Tie 2 signaling pathway plays a critical role in blood vessel development, formation, remodeling, and peripheral nerve regeneration. Therefore, activation strategies of the Tie2 signaling pathway have been developed as potential therapies for ischemic and inflammatory vasculoneural diseases. Here, we developed a human Tie2 agonist antibody (MT-100) that not only resists Angpt2 antagonism and activates Tie2 signaling, but also regulates a novel target, Sushi Repeat Containing Protein X-Linked 2 (Srpx2), to survival of vascular and neuronal cells, reduces the production of reactive oxygen species (ROS), activates the PI3K/AKT/eNOS signaling pathway, increases the expression of neurotrophic factors (NGF, BDNF, and NT3), and ultimately improves the erectile function of diabetic mice. Our findings not only provide new conclusive evidence that the human Tie2 agonist antibody MT-100 may be a promising therapeutic strategy for the treatment of diabetic ED but also create substantial clinical applications for other complications associated with diabetes.
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Project description:To identify the miRNA expressing profiles of TIE2 expressing Monocytes (TEMs), we have employed the Agilent Human miRNA 8×60K (Design ID:046064) microarray. Human peripheral blood mononuclear cells (PBMCs) in venous blood from healthy donors were isolated by Lymphoprep (Axis-Shield, Norway). Human monocytes in PBMCs, identified as cells that expressed CD14, were enriched by positive immunomagnetic selection using anti-CD14 MicroBeads (Miltenyi, Germany). TEMs (TIE2+CD14+) and TIE2-Monocytes (Tie2-CD14+) were then isolated by FACS-sorting (Aria II, BD Biosciences) using FITC-conjugated anti-CD14 (BD Biosciences, USA) and APC-conjugated anti-TIE2 (R&D System, USA) antibodies.Three TEMs samples together with their paried TIE2-Monocytes were detected.
2017-05-19 | GSE68322 | GEO
Project description:To identify the gene expressing profiles of TIE2 expressing Monocytes(TEMs), we have employed the Agilent lncRNA Gene Expression 4Ã180K(Design ID:042818) microarray. Human peripheral blood mononuclear cells (PBMCs) in venous blood from healthy donors were isolated by Lymphoprep (Axis-Shield, Norway). Human monocytes in PBMCs, identified as cells that expressed CD14, were enriched by positive immunomagnetic selection using anti-CD14 MicroBeads (Miltenyi, Germany). TEMs (TIE2+CD14+) and TIE2-Monocytes (Tie2-CD14+) were then isolated by FACS-sorting (Aria II, BD Biosciences) using FITC-conjugated anti-CD14 (BD Biosciences, USA) and APC-conjugated anti-TIE2 (R&D System, USA) antibodies.Three TEMs samples together with their paried TIE2-Monocytes were detected.Expressions of sixteen genes (CDKN1A, FDXR, SESN1, BBC3 and PHPT1) from this signature was quantified in the same RNA samples by real-time PCR, confirming low variability between donors as well as the predicted radiation response pattern. The gene expressions of three independent paried TEMs and TIE2- Monocytes samples from different donors were measured.
2017-05-17 | E-GEOD-57783 | biostudies-arrayexpress
Project description:To identify the gene expressing profiles of TIE2 expressing Monocytes(TEMs), we have employed the Agilent lncRNA Gene Expression 4×180K(Design ID:042818) microarray. Human peripheral blood mononuclear cells (PBMCs) in venous blood from healthy donors were isolated by Lymphoprep (Axis-Shield, Norway). Human monocytes in PBMCs, identified as cells that expressed CD14, were enriched by positive immunomagnetic selection using anti-CD14 MicroBeads (Miltenyi, Germany). TEMs (TIE2+CD14+) and TIE2-Monocytes (Tie2-CD14+) were then isolated by FACS-sorting (Aria II, BD Biosciences) using FITC-conjugated anti-CD14 (BD Biosciences, USA) and APC-conjugated anti-TIE2 (R&D System, USA) antibodies.Three TEMs samples together with their paried TIE2-Monocytes were detected.Expressions of sixteen genes (CDKN1A, FDXR, SESN1, BBC3 and PHPT1) from this signature was quantified in the same RNA samples by real-time PCR, confirming low variability between donors as well as the predicted radiation response pattern.
2017-05-17 | GSE57783 | GEO
Project description:Analysis of genes deregulated due to heterozygous overexpression of Foxf1 in endothelial and hematopoietic cells using Tie2-cre in embryonic day 18.5 mouse lungs. Total RNA obtained from three ROSA26Foxf1; Tie2-cre mouse lungs compared to three control ROSA26-lox-stop-lox (LSL) -Foxf1 mouse lungs.
2016-09-01 | E-GEOD-77881 | biostudies-arrayexpress
Project description:The ang1-Tie2 pathway is required for normal vascular development, but its molecular effectors are not well-defined during cardiac ontogeny. Here we show that endocardial specific attenuation of Tie2 results in mid-gestation lethality due to heart defects associated with a hyperplastic but simplified trabecular meshwork (fewer but thicker trabeculae). Reduced proliferation and production of endocardial cells (ECs) following endocardial loss of Tie2 results in decreased endocardial sprouting required for trabecular assembly and extension. The hyperplastic trabeculae result from enhanced proliferation of trabecular cardiomyocyte (CMs), which is associated with upregulation of Bmp10, increased retinoic acid (RA) signaling, and Erk1/2 hyperphosphorylation in the myocardium. Intriguingly, myocardial phenotypes in Tie2-cko hearts could be partially rescued by inhibiting in utero RA signaling with pan-retinoic acid receptor antagonist BMS493. These findings reveal two complimentary functions of endocardial Tie2 during ventricular chamber formation: ensuring normal trabeculation by supporting EC proliferation and sprouting, and preventing hypertrabeculation via suppression of RA signaling in trabecular CMs.
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