A5000377104- Cancer, Hypoxia, and Metabolism
- Circadian rhythm and melatonin
- Cardiovascular Function and Risk Factors
- Angiogenesis and VEGF in Cancer
- Immune cells in cancer
- Reproductive System and Pregnancy
- Fibroblast Growth Factor Research
- Cardiomyopathy and Myosin Studies
- RNA modifications and cancer
- Adipose Tissue and Metabolism
- Cardiac Imaging and Diagnostics
- Endometriosis Research and Treatment
- Blood Pressure and Hypertension Studies
- Heart Failure Treatment and Management
- Epigenetics and DNA Methylation
- Spaceflight effects on biology
- Cardiovascular Disease and Adiposity
- Diabetes Treatment and Management
- Advanced MRI Techniques and Applications
- Mitochondrial Function and Pathology
- Pulmonary Hypertension Research and Treatments
- Autophagy in Disease and Therapy
- Cardiac Fibrosis and Remodeling
- Amino Acid Enzymes and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
The University of Tokyo
2015-2025
Jichi Medical University
2020-2025
University of Tokyo Hospital
2016-2025
Takeda (Japan)
2024-2025
Takeda (United States)
2018-2024
Kubota (Japan)
2024
International University of Health and Welfare
2024
Jichi Medical University Hospital
2022
Japan Science and Technology Agency
2017
The University of Texas at Dallas
2014
Hypoxic response and inflammation both involve the action of hypoxia-inducible transcription factors HIF-1α HIF-2α. Previous studies have revealed that HIF-α proteins are in a number aspects similarly regulated post-translationally. However, functional interrelationship these two isoforms remains largely unclear. The polarization macrophages controls functionally divergent processes; one is nitric oxide (NO) production, which turn controlled part by HIF factors. We show here can be...
Abstract In severely hypoxic condition, HIF-1α-mediated induction of Pdk1 was found to regulate glucose oxidation by preventing the entry pyruvate into tricarboxylic cycle. Monocyte-derived macrophages, however, encounter a gradual decrease in oxygen availability during its migration process inflammatory areas. Here we show that HIF-1α-PDK1-mediated metabolic changes occur mild hypoxia, where mitochondrial cytochrome c oxidase activity is unimpaired, suggesting mode glycolytic reprogramming....
Abstract Vascular/parenchymal crosstalk is increasingly recognized as important in the development and maintenance of healthy vascularized tissues. The retina an excellent model which to study role cell type‐specific contributions process blood vessel neuronal growth. During retinal vascular development, glial cells such astrocytes provide template over endothelial migrate form network, hypoxia‐regulated growth factor (VEGF) has been demonstrated play a critical this well pathological...
Productive angiogenesis, a prerequisite for tumour growth, depends on the balanced release of angiogenic and angiostatic factors by different cell types within hypoxic tumours. Natural killer (NK) cells kill cancer infiltrate areas. Cellular adaptation to low oxygen is mediated Hypoxia-inducible (HIFs). We found that deletion HIF-1α in NK inhibited growth despite impaired killing. Tumours developing these conditions were characterised high-density network immature vessels, severe...
Excessive acetaminophen (APAP) use is one of the most common causes acute liver failure. Various types cell death in damaged are linked to APAP-induced hepatotoxicity, and, these, necrotic hepatocytes has been shown be involved disease pathogenesis. Until recently, necrosis was commonly considered a random and unregulated form death; however, recent studies have identified previously unknown programmed called receptor-interacting protein kinase (RIPK)-dependent (or necroptosis), which...
Abstract Background Type 2 diabetes mellitus (T2DM) greatly increases the risks of cardiovascular disease and heart failure. In particular, left ventricular diastolic dysfunction that develops from early stages T2DM is an important factor in onset exacerbation The effect sodium-glucose cotransporter inhibitors on function has not been elucidated. We have performed first prospective study effects canagliflozin T2DM. Methods This was to evaluate additional treatment with for 3 months patients...
Abstract Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small lung cancer (NSCLC) distinct in their histological, molecular clinical presentation. However, metabolic signatures specific to individual NSCLC remain unknown. Here, we perform an integrative analysis human tumour samples, patient-derived xenografts, murine model NSCLC, lines The Cancer Genome Atlas (TCGA) reveal a markedly elevated expression GLUT1 glucose transporter SqCC, which...
Hypoxia has long been implicated in the pathogenesis of fibrotic diseases. Aberrantly activated myofibroblasts are primary pathological driver progression, yet how various microenvironmental influences, such as hypoxia, contribute to their sustained activation and differentiation is poorly understood. As a defining feature hypoxia its impact on cellular metabolism, we sought investigate hypoxia-induced metabolic reprogramming affects myofibroblast test preclinical efficacy targeting...
Autosomal dominant polycystic kidney disease (ADPKD) constitutes the most inherited disease. Mutations in PKD1 and PKD2 genes, encoding polycystin 1 2 Ca2+ ion channels, respectively, result tubular epithelial cell-derived renal cysts. Recent clinical studies demonstrate oxidative stress to be present early ADPKD. Mitochondria comprise primary reactive oxygen species source also their main effector target; however, pathophysiological role of mitochondria ADPKD remains uncharacterized. To...
Abstract The fibrogenic response in tissue-resident fibroblasts is determined by the balance between activation and repression signals from tissue microenvironment. While molecular pathways which transforming growth factor-1 (TGF-β1) activates pro-fibrogenic mechanisms have been extensively studied are recognized critical during fibrosis development, factors regulating TGF-β1 signaling poorly understood. Here we show that macrophage hypoxia suppresses excessive a heart via oncostatin-m (OSM)...
This study investigates Actinomyces odontolyticus's role in colorectal cancer initiation.The bacterium secretes lipoteichoic acid-rich membrane vesicles, inducing chronic inflammation, nuclear factor-κB signaling, and excessive reactive oxygen species colonic epithelial cells.These processes result DNA damage, potentially contributing to development.
Endothelial PAS domain protein 1 (EPAS1) is a basic-helix-loop-helix/PAS transcription factor that expressed preferentially in vascular endothelial cells. EPAS1 shares high homology with hypoxia-inducible factor-1alpha (HIF-1alpha) and reported to transactivate growth (VEGF), fetal liver kinase-1 (Flk-1), Tie2 promoters. In this study, we analyzed the role of process angiogenesis. Using microarray technology, looked for target genes regulated by A total 130 were upregulated EPAS1, including...
Central to cellular responses hypoxic environment is the hypoxia-inducible factor (HIF) transcriptional control system. A role for HIF-2α was investigated in a model of renal ischemia-reperfusion injury (IRI) associated with oxidative stress using knockdown mice. In these mice, expression approximately one half that wild-type whereas HIF-1α equivalent. mice were more susceptible IRI, as indicated by elevated blood urea nitrogen levels and semiquantitative histologic analysis. Immunostaining...
Cardiovascular diseases are closely related to circadian rhythm, which is under the control of an internal biological clock mechanism. Although a exists not only in hypothalamus but also each peripheral tissue, relevance remains be elucidated. In this study we searched for clock-controlled genes vascular endothelial cells using microarray technology. The expression total 229 was up-regulated by CLOCK/BMAL2. Among that identified, examined thrombomodulin (TM) gene further, because TM integral...
A key adaptation to environmental hypoxia is an increase in erythropoiesis, driven by the hormone erythropoietin (EPO) through what traditionally thought be primarily a renal response. However, both neurons and astrocytes (the largest subpopulation of glial cells CNS) also express EPO following ischemic injury, this response known ameliorate damage brain. To investigate role as component systemic hypoxia, we created astrocyte-specific deletions murine genes encoding hypoxia-inducible...
Although it has been reported that hypoxia inducible factor 2 α (Hif2a), a major transcriptional by low oxygen tension, is expressed in the mouse uterus during embryo implantation, its role pregnancy outcomes remains unclear. This study aimed to clarify functions of uterine HIF using transgenic models. Mice with deletion Hif2a whole (Hif2a-uKO mice) showed infertility due implantation failure. Supplementation progesterone (P4) and leukemia inhibitory (LIF) restored decidual growth arrest...
Erythropoietin (Epo) is produced in the kidney and liver a hypoxia-inducible manner via activation of transcription factors (HIFs) to maintain oxygen homeostasis. Accelerating Epo production hepatocytes one plausible therapeutic strategy for treating anemia caused by diseases. To elucidate regulatory mechanisms hepatic production, we analyzed mouse lines harboring liver-specific deletions genes encoding HIF-prolyl-hydroxylase isoforms (PHD1, PHD2, PHD3) that mediate inactivation HIF1α HIF2α...