- Angiogenesis and VEGF in Cancer
- Pluripotent Stem Cells Research
- Zebrafish Biomedical Research Applications
- Renal and related cancers
- Effects and risks of endocrine disrupting chemicals
- Congenital heart defects research
- CRISPR and Genetic Engineering
- Kruppel-like factors research
- Axon Guidance and Neuronal Signaling
- Lymphatic System and Diseases
- Carcinogens and Genotoxicity Assessment
- Epigenetics and DNA Methylation
- Marine Biology and Environmental Chemistry
- Animal Genetics and Reproduction
- Cell Adhesion Molecules Research
- Cancer, Hypoxia, and Metabolism
- Reproductive Biology and Fertility
- Toxic Organic Pollutants Impact
- Sperm and Testicular Function
- Environmental Toxicology and Ecotoxicology
- Neurogenesis and neuroplasticity mechanisms
- Receptor Mechanisms and Signaling
- Genetics and Neurodevelopmental Disorders
- Birth, Development, and Health
- Neonatal Respiratory Health Research
Shiga University of Medical Science
2016-2025
Kyoto University
2019-2024
University of Tsukuba
2007-2023
National Institute for Physiological Sciences
2022
Nippon Medical School
2021
The University of Tokyo
2020
Japan Science and Technology Agency
2006-2019
RCA (United States)
2016
Tohoku University
1994-2015
Shiga University
2014
We have isolated and characterized a cDNA for novel Per-Arnt/AhR-Sim basic helix–loop–helix (bHLH-PAS) factor that interacts with the Ah receptor nuclear translocator (Arnt), its predicted amino acid sequence exhibits significant similarity to hypoxia-inducible 1α (HIF1α) Drosophila trachealess ( dTrh ) gene product. The HIF1α-like (HLF) encoded by bound hypoxia-response element (HRE) found in enhancers of genes erythropoietin, vascular endothelial growth (VEGF), various glycolytic enzymes,...
Background: The aryl hydrocarbon receptor (AhR or dioxin receptor) is a ligand‐activated transcription factor that considered to mediate pleiotropic biological responses such as teratogenesis, tumour promotion, epithelial hyperplasia and the induction of drug‐metabolizing enzymes environmental contaminants usually represented by 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin (TCDD). In contrast role AhR in regulatory mechanism xenobiotic‐metabolizing enzymes, there no direct proof involved...
Ah receptor (AhR) is a ligand-activated transcription factor that mediates pleiotropic effects of environmental pollutants such as 2,3,7,8-tetrachlorodibenzo- p -dioxin on host animals. In addition to induction drug-metabolizing enzymes, the liganded AhR complex was found activate gene expression designated repressor (AhRR), which inhibits function by competing with for dimerizing Arnt and binding XRE sequence. Thus, AhRR form regulatory circuit in xenobiotic signal transduction pathway...
The subventricular zone (SVZ) of the adult brain contains neural stem cells that have capacity to regenerate new neurons after various insults. Brain ischemia causes damage tissue and induces regeneration together with angiogenesis. We previously reported that, ischemic injury in mice, SVZ-derived progenitor (NPCs) migrate into striatum, these NPCs are frequently associated blood vessels regenerating tissue. Here we studied role during more detail. BrdU administration experiments revealed...
The genetic difference in the susceptibility of mice to environmental toxicities induced by dioxin and related chemicals is governed polymorphism arylhydrocarbon receptor (AhR) (Poland, A., Knutson, C. (1982) Annu. Rev. Pharmacol. Toxicol. 22, 517-554). cDNA cloning AhR from responder (C57BL/6) non-responder (DBA/2J) allowed us analyze structure function these AhRs. Both AhRs, which were expressed COS-7 cells transfected with their expression plasmids, showed a clear 9 S complex...
We isolated mouse cDNA clones (Arnt2) that are highly similar to but distinct from the aryl hydrocarbon receptor (AhR) nuclear translocator (Arnt). The composite covered a 2,443-bp sequence consisting of putative 2,136-bp open reading frame encoding polypeptide 712 amino acids. predicted Arnt2 carries characteristic basic helix-loop-helix (bHLH)/PAS motif in its N-terminal region with close similarity (81% identity) Arnt and has an overall identity 57% Arnt. Biochemical properties...
Mouse embryos mutant for the VEGF receptor, VEGFR2, Flk-1, or Kdr, fail to form both endothelial and hematopoietic cells, suggesting a possible role in common progenitor lineages. The transcription factor Tal1 (Scl), is not expressed Flk1 −/− embryos, consistent with downstream pathway. We tested whether expression of under promoter was sufficient rescue loss cells mutants. Only partial hematopoiesis development observed vivo. However, − /Tal1 embryonic stem (ES) were capable blast colony...
The glomerular filtration barrier separates the blood from urinary space and consists of two major cell types: podocytes fenestrated endothelial cells. Mesangial cells sit between capillary loops provide structural support. Proliferation loss mesangial both are central findings in a number renal diseases, including diabetic nephropathy mesangiolysis, respectively. Using cell-specific gene targeting, it was shown previously that vascular growth factor A (VEGF-A) production by is required for...
Nitric oxide (NO) is known to have various biologic and pathophysiologic effects on organisms. The molecular mechanisms by which NO exerts harmful are unknown, although O 2 radicals ions that result from reactivity of presumed be involved. Here we report adaptive cellular response controlled the transcription factor hypoxia-inducible 1 (HIF-1) in hypoxia suppressed NO. Induction erythropoietin glycolytic aldolase A mRNAs hypoxically cultured Hep3B cells, a human hepatoma cell line, was...
In the central nervous system, endothelial cells (ECs) and pericytes (PCs) of blood vessel walls cooperatively form a physical chemical barrier to maintain neural homeostasis. However, in diabetic retinopathy (DR), loss PCs from is assumed cause breakdown blood-retina (BRB) subsequent vision-threatening vascular dysfunctions. Nonetheless, lack adequate DR animal models has precluded disease understanding drug discovery. Here, by using an anti-PDGFRβ antibody, we show that transient...
Highlights•Mouse spermatogenic stem cells (SSCs) migrate among their differentiating progeny•Lymphatic endothelial near vasculature secrete FGFs that act as SSC mitogens•SSCs tune self-renewal and differentiation in response to FGF consumption•Competition for limited supply of mitogen (FGFs) regulates density homeostasisSummaryIn many tissues, homeostasis is maintained by physical contact between an anatomically defined niche. However, how cell achieved environments where are motile...
In pluripotent stem cells (PSCs), there are 2 types: naive and primed. Only the type has capacity for producing chimeric offspring. Mouse PSCs naive, but human in primed state. Previously reported porcine appear this study, putative porcine-induced (iPSCs) were generated. Porcine embryonic fibroblasts transduced with retroviral vectors expressing Yamanaka's 4 genes. Emergent colonies propagated presence of leukemia inhibitory factor (pLIF) forskolin. The expressed pluripotency markers formed...
Highlights•A portion of pericytes in the skin vasculature has a hematopoietic/myeloid origin•Depletion myeloid lineage causes defective pericyte development•TGF-β signaling controls differentiation progenitors to pericytesSummaryMural cells (pericytes and vascular smooth muscle cells) are essential for regulation networks maintenance integrity, but their origins diverse different tissues not known organs that arise from ectoderm, such as skin. Here, we show tissue-localized contribute...
From a cDNA library of mouse skeletal muscle, we have isolated Sim1 (mSim1) encoding polypeptide 765 amino acids with striking acid identify in basic helix-loop-helix (89% identify) and PAS (89 % domains to previously identified mSim2, although the carboxy-terminal third molecule did not show any similarity mSim2 or Drosophila Sim (dSim). Yeast two-hybrid analysis coimmunoprecipitation experiments demonstrated that both mSim gene products interacted Arnt even more efficiently than AhR,...
Xenobiotic responsive element (XRE) is an inducible enhancer that drives expression of P-4501A1 gene in response to xenobiotic inducers. The XRE-binding factor appears the nuclei Hepa-1 cells treated with 3-methylcholanthrene (3-MC). Association Ah receptor and Arnt (Ah nuclear translocator) complex was examined by anti-Ah antibodies. Both antibodies inhibited sequence-specific activity extracts from 3-MC-treated cytosolic fraction which prepared nontreated vitro 3-MC. These results indicate...
Vascular development depends on transforming growth factor beta (TGFbeta), but whether signalling of this protein is required for the endothelial cells (ECs), vascular smooth muscle (VSMCs) or both unclear. To address this, we selectively deleted type I (ALK5, TGFBR1) and II (TbetaRII, TGFBR2) receptors in mice. Absence either receptor ECs resulted defects yolk sac, as seen mice lacking all cells, causing embryonic lethality at day (E)10.5. Deletion TbetaRII specifically VSMCs also sac;...