A5045784267- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- Histone Deacetylase Inhibitors Research
- Cancer-related gene regulation
- Cancer, Hypoxia, and Metabolism
- Adipose Tissue and Metabolism
- Angiogenesis and VEGF in Cancer
- Developmental Biology and Gene Regulation
- Atherosclerosis and Cardiovascular Diseases
- RNA modifications and cancer
- Adipokines, Inflammation, and Metabolic Diseases
- Immune cells in cancer
- Ferroptosis and cancer prognosis
- Congenital heart defects research
- Vagus Nerve Stimulation Research
- Cell Adhesion Molecules Research
- Monoclonal and Polyclonal Antibodies Research
- Biomarkers in Disease Mechanisms
- Protease and Inhibitor Mechanisms
- Radiopharmaceutical Chemistry and Applications
- Cholesterol and Lipid Metabolism
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Nicotinic Acetylcholine Receptors Study
- dental development and anomalies
The University of Tokyo
2015-2024
Japan Agency for Medical Research and Development
2019
Japan Radioisotope Association
2014
Cancer Genetics (United States)
2013
Roswell Park Comprehensive Cancer Center
2013
Tokyo Medical and Dental University
2013
Jobu University
2013
Systems Biology Institute
2011
Beth Israel Deaconess Medical Center
2005-2010
Center for Vascular Biology Research
2006
Hypoxia-inducible factor 1 (HIF1) is a master regulator of adaptive gene expression under hypoxia. However, role for HIF1 in the epigenetic regulation remains unknown. Genome-wide analysis binding sites (chromatin immunoprecipitation [ChIP] with deep sequencing) endothelial cells clarified that mainly binds to intergenic regions distal from transcriptional starting both normoxia and Next, we examined temporal profile hypoxic conditions by using DNA microarrays. We early hypoxia-responsive...
Human atherosclerotic lesions overexpress the lysosomal cysteine protease cathepsin S (Cat S), one of most potent mammalian elastases known. In contrast, atheromata have low levels endogenous Cat inhibitor cystatin C compared with normal arteries, suggesting involvement this in atherogenesis. The present study tested hypothesis directly by crossing S-deficient (CatS(-/-)) mice LDL receptor-deficient (LDLR(-/-)) that develop atherosclerosis on a high-cholesterol diet. Compared LDLR(-/-) mice,...
Human atherosclerotic lesions overexpress the lysosomal cysteine protease cathepsin S (Cat S), one of most potent mammalian elastases known. In contrast, atheromata have low levels endogenous Cat inhibitor cystatin C compared with normal arteries, suggesting involvement this in atherogenesis. The present study tested hypothesis directly by crossing S–deficient (CatS–/–) mice LDL receptor–deficient (LDLR–/–) that develop atherosclerosis on a high-cholesterol diet. Compared LDLR–/– mice,...
Heme oxygenase-1 (HO-1), the rate-limiting enzyme of heme degradation, has recently been considered to have protective roles against various pathophysiological conditions. Since we demonstrated that HO-1 overexpression inhibits atherosclerotic formation in animal models, examined effect HO modulation on proinflammatory cytokine production, endothelial NO synthase (eNOS) expression, and endothelium-dependent vascular relaxation responses.After induction by arginate (HA), cell cultures were...
Genome-wide studies reveal that transcription by RNA polymerase II (Pol II) is dynamically regulated. To obtain a comprehensive view of single cycle, we switched on five long human genes (>100 kbp) with tumor necrosis factor-alpha (TNFalpha) and monitored (using microarrays, fluorescence in situ hybridization, chromatin immunoprecipitation) the appearance nascent RNA, changes binding Pol two insulators (the cohesin subunit RAD21 CCCTC-binding factor CTCF), modifications histone H3....
Engaging inhibitory FcγRIIb by Fc region has been recently reported to be an attractive approach for improving the efficacy of antibody therapeutics. However, previously S267E/L328F variant with enhanced binding affinity FcγRIIb, also enhances FcγRIIaR131 allotype a similar degree because and are structurally similar. In this study, we applied comprehensive mutagenesis structure-guided design based on crystal structure Fc/FcγRIIb complex identify novel selectively over both FcγRIIaH131. This...
Large-scale clinical trials have demonstrated significant reductions in cardiovascular events following statin therapy. The observed benefit of therapy, however, may be greater these than is to expected from lowering lipid levels alone. In order clarify the mechanism by which statins prevent vascular wall cells, we investigated changes gene expression profiles after incubation with atorvastatin or pitavastatin cultured human umbilical vein endothelial cells using DNA microarrays. Statins...
DNA microarray gene expression analysis was conducted in human umbilical vein endothelial cells (HUVECs) and coronary artery (HCAECs) exposed to laminar or turbulent shear stress. Approximately 3% of the total 5600 HUVECs HCAECs increased their more than two-fold decreased it less half static control response an arterial level stress (15 dynes/cm2 for 24 hours). The proportions shear-stress-responsive genes around 2% under venous (1.5 dynes/cm2) both cell lines. Turbulent 1.5 altered 1.1%...
It is widely assumed that active RNA polymerases track along their templates to produce a transcript. We test this using chromosome conformation capture and human genes switched on rapidly synchronously by tumour necrosis factor alpha (TNFalpha); one 221 kbp SAMD4A, which polymerase takes more than 1 h transcribe. Ten minutes after stimulation, the SAMD4A promoter comes together with other TNFalpha-responsive promoters. Subsequently, these contacts are lost as new downstream ones appear;...
Antiangiogenic strategies can be effective for cancer therapy, but like all therapies resistance poses a major clinical challenge. Hypoxia and nutrient starvation select aggressive qualities that may render tumors resistant to antiangiogenic attack. Here, we show hypoxia cooperate drive tumor aggressiveness through epigenetic regulation of the histone demethylase JMJD1A (JHDM2A; KDM3A). In cells rendered long-term starvation, documented stimulation AKT phosphorylation, cell morphologic...
Synergistic transcriptional activation by different stimuli has been reported along with a diverse array of mechanisms, but the full scope these mechanisms yet to be elucidated.We present detailed investigation hypoxia-inducible factor (HIF) 1 dependent gene expression in endothelial cells which suggests importance crosstalk between peroxisome proliferator-activated receptor (PPAR) β/δ and HIF signaling axes. A migration assay shows synergistic interaction two stimuli, we identify...
Murine macrophage RAW264 were investigated for their response to lipid-free apolipoproteins. Preincubation of the cells with 300 μM dibutyryl cyclic (dBc) AMP 16 h induced specific binding apolipoprotein (apo) A-I and apoA-I-mediated HDL formation cellular lipids, neither which was detected in absence dBcAMP. Dose-dependent changes apoA-I cholesterol release largely superimposable. ApoA-II also mediated lipid after treatment dBcAMP effectively displaced cells. In contrast, efflux...
Although studies of the differentiation from mouse embryonic stem (ES) cells to vascular endothelial (ECs) provide an excellent model for investigating molecular mechanisms underlying development, temporal dynamics gene expression and chromatin modifications have not been well studied. Herein, using transcriptomic epigenomic analyses based on H3K4me3 H3K27me3 at a genome-wide scale, we analysed EC steps ES crucial epigenetic unique ECs. We determined that Gata2, Fli1, Sox7 Sox18 are master...
Significance Statement The detailed role of neural activity in inflammatory diseases is still unclear because it varies according to the disease situation and responsible cell types. This study shows that activation β 2-adrenergic receptor (Adrb2) signaling macrophages induces expression T Ig mucin domain 3 ( Tim3 ), which contributes anti-inflammatory phenotypic alterations. Experiments using conditional knockout mice reveal macrophage Adrb2 directly mitigates LPS-induced systemic...
Abstract Activation of the cholinergic anti-inflammatory pathway (CAP) via vagus nerve stimulation has been shown to improve acute kidney injury in rodent models. While alpha 7 nicotinic acetylcholine receptor (α7nAChR) positive macrophages are thought play a crucial role this pathway, their vivo significance not fully understood. In study, we used macrophage-specific α7nAChR-deficient mice confirm direct activation α7nAChRs macrophages. Our findings indicate that administration GTS-21, an...