A5051292777- Cerebrovascular and genetic disorders
- Retinal Diseases and Treatments
- Retinal Imaging and Analysis
- Protease and Inhibitor Mechanisms
- Retinal Development and Disorders
- Pluripotent Stem Cells Research
- Connective Tissue Growth Factor Research
- Advanced Glycation End Products research
- Porphyrin and Phthalocyanine Chemistry
- Photodynamic Therapy Research Studies
- Immune Cell Function and Interaction
- Neurological diseases and metabolism
- Nanoplatforms for cancer theranostics
- Mitochondrial Function and Pathology
- Microtubule and mitosis dynamics
- Genetics and Neurodevelopmental Disorders
- Nuclear Receptors and Signaling
- Moyamoya disease diagnosis and treatment
- Chromatography in Natural Products
- T-cell and B-cell Immunology
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Retinoids in leukemia and cellular processes
- Congenital heart defects research
- Glaucoma and retinal disorders
Nara Institute of Science and Technology
2016-2025
Kyoto University
1992-2003
RIKEN Center for Computational Science
2003
Ideta Eye Hospital
1995
ABSTRACT The RBP-Jк protein is a transcription factor that recog-nizes the sequence C(T)GTGGGGA. gene highly conserved in wide variety of species and Drosophila homologue has been shown to be identical Suppressor Hairless [Su(H)] which plays important roles development peripheral nervous system. To explore function mouse embryo-genesis, mutation was introduced into functional embryonic stem (ES) cells by homologous recombination. Null mutant ES survived but null mice showed lethality before...
Abstract Tissue fibrosis and organ dysfunction are hallmarks of age-related diseases including heart failure, but it remains elusive whether there is a common pathway to induce both events. Through single-cell RNA-seq, spatial transcriptomics, genetic perturbation, we elucidate that high-temperature requirement A serine peptidase 3 (Htra3) critical regulator cardiac failure by maintaining the identity quiescent fibroblasts through degrading transforming growth factor-β (TGF-β). Pressure...
HtrA1, a member of the mammalian HtrA serine protease family, has highly conserved domain followed by PDZ domain. Because HtrA1 is secretory protein and another functional with homology to follistatin, we examined whether functions as an antagonist Tgfbeta family proteins. During embryo development, mouse was expressed in specific areas where signaling proteins plays important regulatory roles. The GST-pulldown assay showed that binds broad range proteins, including Bmp4, Gdf5, Tgfbetas...
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in elderly. Wet AMD includes typical choroidal neovascularization (CNV) and polypoidal vasculopathy (PCV). The etiology pathogenesis CNV PCV are not well understood. Genome-wide association studies have linked a multifunctional serine protease, HTRA1, to AMD. However, precise role HTRA1 remains elusive. By transgenically expressing human mouse retinal pigment epithelium, we showed that increased induced...
The expression of mouse HtrA1 is developmentally regulated and restricted in embryo tissues which depend largely on TGF-beta signaling for their differentiation. We examined whether HtrA3, another HtrA family member very close to HtrA1, shows similar patterns. HtrA3 -1 were expressed mostly the same embryonic organs but exhibited complementary patterns various tissues; lens epithelial cells day 12.5 whereas ciliary body pigment retina HtrA1. In vertebrae 14.5 embryo, was tail region,...
Genome-wide association study (GWAS) has identified genetic variants in the promoter region of high temperature requirement factor A1 (HTRA1) gene associated with age-related macular degeneration (AMD). As a secreted serine protease, HTRA1 been reported to interact members transforming growth factor-β (TGF-β) family and regulate their signaling pathways. Growth differentiation 6 (GDF6), member TGF-β family, is involved ectoderm patterning eye development. Mutations GDF6 have abnormal...
The transcription factor recombination signal sequence-binding protein Jκ (RBP-J) is a key downstream element in the signaling pathway of all four mammalian Notch receptors that are critically involved control embryonic and adult development. RBP-J-deficient mice display complex defects die around day 9.5 postcoitum. Here, we investigate function RBP-J development mesodermal cell lineages by using OP9 stroma coculture system. stem (ES) cells gave rise to cardiomyocytes, endothelial cells,...
Background Development of the pancreas and nervous tissues is regulated by common transcription factors. A basic helix‐loop‐helix protein, p48 factor 1 (PTF1), essential for differentiation exocrine acinar cells. Results We isolated PTF1 from 9.5‐day mouse embryos as a binding protein RBP‐Jκ, mediator Notch signalling. bound to RBP‐Jκ more strongly than in distinct way Notch1. In 9.5–12.5 day embryos, was expressed dorsal part neural tube well pancreatic buds. Two lines evidence suggested...
HtrA1, a member of the mammalian HtrA (high temperature requirement A) serine protease family, has highly conserved domain followed by PDZ domain. Accumulating evidence indicated that domains regulate activity proteins. We searched for binding partners mouse HtrA1 yeast two-hybrid screening, and isolated proteins were recognized through their C-terminal ends with core consensus Phi-X-Phi-[V/L/F/A]-COOH sequence (where Phi is hydrophobic/non-polar amino acid). C-propeptides fibrillar...
The high-temperature requirement A1 (HTRA1), a serine protease, has been demonstrated to play pivotal role in the extracellular matrix (ECM) and reported be associated with pathogenesis of age-related macular degeneration (AMD). To delineate its retina, phenotype homozygous Htra1-KO (Htra1-/-) mice was characterized examine effect Htra1 loss on retina retinal pigment epithelium (RPE) age. ablation led significant reduction rod cone photoreceptor function, primary abnormalities followed by...
Deficiency of caytaxin results in hereditary ataxia or dystonia humans, mice and rats. Our yeast two-hybrid screen identified kinesin light chains (KLCs) as caytaxin-binding proteins. The tetratricopeptide-repeat region KLC1 recognizes the ELEWED sequence (amino acids 115-120) caytaxin. This motif is conserved among BNIP-2 family members other KLC-interacting cargo proteins such calsyntenins. Caytaxin associates with heavy (KHCs) indirectly by binding to KLCs, suggesting that binds...
Palladium(II) complexes of glycoconjugated porphyrin and pyrrolidine-fused chlorin were prepared to examine sugar heavy atom effects on in vitro photocytotoxicity. Cellular uptake into HeLa cells was enhanced by introducing units regardless other features, such as the central ion (free base or palladium(II) ion) ring structure (porphyrin chlorin). The complex (PdPC2) exerted an excellent degree photocytotoxicity not only cells, but also metastatic B16-BL6 weakly B16F1 4T1 cells. However,...
Dry age-related macular degeneration (AMD) accounts for over 85% of AMD cases in the United States, whereas Japanese patients predominantly progress to wet or polypoidal choroidal vasculopathy. Recent genome-wide association studies have revealed a strong between and an insertion/deletion sequence ARMS2 (age-related maculopathy susceptibility 2) HTRA1 (high temperature requirement A serine peptidase 1) genes. Transcription regulator activity was localized mouse retinas using heterozygous...
trans-Bisthioglycosylated tetrakis(fluorophenyl)chlorin (7) was designed as a powerful photodynamic therapy (PDT) photosensitizer based on the findings of our systematic studies. We show here that trans-bisthioglycosylated structure 7 enhanced its uptake by HeLa cells and chlorin ring increased efficiency reactive oxygen species generation under standard condition photocytotoxicity test. The versatility in PDT treatment established using weakly metastatic B16F1 melanoma cells, 4T1 breast...
Astrocytes perform a wide array of physiological functions, including structural support, ion exchange, and neurotransmitter uptake. Despite this diversity, molecular markers that label subpopulations astrocytes are limited, mechanisms generate distinct astrocyte subtypes remain unclear. Here we identified serine protease high temperature requirement A 1 (HtrA1), bone morphogenetic protein 4 signaling regulated protein, as novel marker forebrain astrocytes, but not neural stem cells, in...
Abstract Vascular smooth muscle cell (VSMC) dysfunction is a hallmark of small vessel disease, common cause stroke and dementia. Two the most frequently mutated genes in familial disease are HTRA1 NOTCH3 . The protease cleaves ligand JAG1 implying mechanistic link between Notch signaling. Here we report that essential for VSMC differentiation into contractile phenotype. Mechanistically, loss increased protein levels signaling activity VSMC. In addition, enhanced TGFβ-SMAD2/3 activity....
Abstract We have isolated a cDNA clone (RBP-2) for the protein (RBP-J kappa) which binds to immunoglobulin recombination signals with 23-base pair spacers (Matsunami, N., Hamaguchi, Y., Yamamoto, Kuze, K., Kangawa, Matsuo, H., Kawaichi, M., and Honjo, T. (1989) Nature 342, 934-937). During further screening of library from same mouse pre-B cell line (38B9), we second (RBP-2N) differs RBP-2 in its 5' sequence. RNase protection assays indicated that RBP-2N type mRNA was produced 10-20 times...
Increased numbers and improperly positioned centrosomes, aneuploidy or polyploidy, chromosomal instability are frequently observed characteristics of cancer cells. While some aspects these events the checkpoint mechanisms well studied, not all players have yet been identified. As role proteases other than proteasome in tumorigenesis is an insufficiently addressed question, we investigated epigenetic control widely conserved protease HTRA1 phenotypes deregulation. Mouse embryonal fibroblasts...