A5087730031- Gout, Hyperuricemia, Uric Acid
- Pluripotent Stem Cells Research
- RNA Research and Splicing
- DNA Repair Mechanisms
- Amyotrophic Lateral Sclerosis Research
- Cellular Mechanics and Interactions
- Nuclear Structure and Function
- Cancer-related Molecular Pathways
- Congenital heart defects research
- Lipid metabolism and disorders
- Drug Transport and Resistance Mechanisms
- Liver Disease Diagnosis and Treatment
- Molecular Biology Techniques and Applications
- Single-cell and spatial transcriptomics
- Cancer therapeutics and mechanisms
- CRISPR and Genetic Engineering
- Pediatric Urology and Nephrology Studies
- Renal Diseases and Glomerulopathies
- Heat shock proteins research
- RNA and protein synthesis mechanisms
- MRI in cancer diagnosis
- Muscle Physiology and Disorders
- Peroxisome Proliferator-Activated Receptors
- RNA regulation and disease
- Neurogenesis and neuroplasticity mechanisms
Saitama Prefecture
2024
Nara Medical University
2017-2022
Kyoto University
2014
The brainstem is a posterior region of the brain, composed three parts, midbrain, pons, and medulla oblongata. It critical in controlling heartbeat, blood pressure, respiration, all which are life-sustaining functions, therefore, damages to or disorders can be lethal. Brain organoids derived from human pluripotent stem cells (hPSCs) recapitulate course brain development expected useful for medical research on central nervous system disorders. However, existing organoid models limited extent...
Recently, researchers have developed protocols for human cerebral organoids using pluripotent stem cells, which mimic the structure of developing brain. Existing research demonstrated that undergo short cultivation periods, contain astrocytes, neurons, and neural but lacked mature oligodendrocytes, mature, fully functional neurons. In this study, we analyzed induced from H9 embryonic (ES) cells were cultivated as long six months. We observed positive MBP (myelin-basic protein), GAD67...
Abstract Nuclear import receptors (NIRs) not only transport RNA-binding proteins (RBPs) but also modify phase transitions of RBPs by recognizing nuclear localization signals (NLSs). Toxic arginine-rich poly-dipeptides from C9orf72 interact with NIRs and cause nucleocytoplasmic deficit. However, the molecular basis for toxicity toward function as modifiers remains unidentified. Here we show that impede ability to RBPs. Isothermal titration calorimetry size-exclusion chromatography revealed...
Abstract In humans, uric acid is an end-product of purine metabolism. Urate excretion from the human kidney tightly regulated by reabsorption and secretion. At least eleven genes have been identified as renal urate transporters. However, it remains unclear whether all tubular cells express same set Here, we show are divided into three distinct cell populations for handling. Analysis healthy kidneys at single-cell resolution revealed that not expressed Only 32% were related to both secretion,...
Abstract Reverse transcription quantitative PCR (RT-qPCR) is used to quantify gene expression and require standardization with reference genes. We sought identify the genes best suited for experiments that induce osteogenic differentiation from human induced pluripotent stem cells. They were cultured in an undifferentiated maintenance medium after confluence, further 28 days. RT-qPCR was performed on undifferentiation markers, osteoblast osteocyte candidates. The stability of each candidate...
Ischemic stroke is one of the most common neurological diseases. However, impact ischemic on human cerebral tissue remains largely unknown due to a lack brain samples. In this study, we applied organoids derived from induced pluripotent stem cells evaluate effect oxygen-glucose deprivation/reoxygenation (OGD/R). Pathway analysis showed relationships between vitamin digestion and absorption, fat peroxisome proliferator-activated receptor (PPAR) signaling pathway, complement coagulation...
Although several potent bile acid Farnesoid X receptor (FXR) and Takeda G-protein-coupled 5 (TGR5, GPBAR1) dual agonists such as INT-767 have been reported, no non-bile FXR/TGR5 agonist has investigated to date. Therefore, we attempted discover identified some agonists, isonicotinamide derivatives in vitro assay. Compound 20p was evaluated C57BL/6J mice, that were administered a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) consisting of 60 kcal% fat 0.1% methionine by...
The excretion and reabsorption of uric acid both to from urine are tightly regulated by transporters. Metabolic syndrome conditions, such as obesity, hypercholesterolemia, insulin resistance, believed regulate the expression transporters decrease acid. However, mechanisms driving cholesterol impacts on have been unknown. Here, we show that metabolite 27-hydroxycholesterol (27HC) upregulates transporter URAT1 encoded SLC22A12 via estrogen receptors (ER). Transcriptional motif analysis showed...
Dotinurad was developed as a uricosuric agent, inhibiting urate (UA) reabsorption through the UA transporter URAT1 in kidneys. Due to its high selectivity for among renal transporters, we investigated mechanism underlying this by identifying dotinurad binding sites specific URAT1. docked using AutoDock4, utilizing AlphaFold2-predicted structure. The inhibitory effects of on wild-type and mutated at predicted were assessed URAT1-mediated [<sup>14</sup>C]UA uptake <i>Xenopus</i> oocytes. Nine...
Proline:arginine (PR) poly-dipeptides from the GGGGCC repeat expansion in C9orf72 have cytotoxicity and bind intermediate filaments (IFs). However, it remains unknown how PR affect cytoskeletal organization focal adhesion (FA) formation. Here, we show that changes to cytoskeleton FA by result alteration of cell stiffness mechanical stress response. increased junctions branches IF network stiffness. They also changed distribution actin size intracellular calcium concentration. or an inhibitor...
The anticancer agent 5-fluorouracil (5-FU) is cytotoxic and often used to treat various cancers. 5-FU thought inhibit the enzyme thymidylate synthase, which plays a role in nucleotide synthesis has been found induce single- double-strand DNA breaks. ATR Ser/Thr kinase (ATR) principal damage response activated UV– chemotherapeutic drug–induced replication stress, but its cellular responses unclear. In this study, we examined effect of inhibition on sensitivity mammalian cells. Using...
Podocyte injury is a critical step toward the progression of renal disease and often associated with loss slit diaphragm proteins, including Podocin. Although there possibility that extracellular domain these proteins can be target for pathological proteolysis, precise mechanism driving phenomenon remains unknown. Here we show Matriptase, membrane-anchored protein, was activated at podocytes in CKD patients mice, whereas Matriptase inhibitors slowed mouse kidney disease. The could accounted...
Ectopic calcification in the cardiovascular system adversely affects life prognosis. DBA/2 mice experience owing to low expression of Abcc6 as observed pseudoxanthoma elasticum (PXE) patients; however, little is known about its characteristics a model. In this study, we explore suitability sub-strain PXE-like tissue model, and effect bisphosphonate which prevents soft tissues hypercalcemic models was evaluated. The incidence heart compared among several sub-strains between both sexes mice....
Purpose: Heat shock induces DNA double-strand breaks (DSBs) in mammalian cells. Mammalian cells are capable of repairing DSBs by utilising the homologous recombination (HR) pathway. Breast cancer susceptibility gene 2 (BRCA2) is known to regulate HR Here, we investigate role BRCA2 damage induced heat shock.Materials and methods: Chinese hamster lung fibroblast cell lines human tongue squamous carcinoma SAS were used. RAD51 foci formation assay was used as an indicator. sensitivity analysed...
ABSTRACT Low-complexity (LC) domains of proteins are found in about one fifth human proteome, and a group LC-domains form labile cross-β polymers liquid-like droplets. Polymers droplets formed from dynamically regulated by posttranslational modifications molecular chaperones including nuclear transport receptors. Repeat expansion the first intron gene designated C9orf72 , which is most prevalent familial amyotrophic lateral sclerosis (ALS), causes nucleocytoplasmic deficit, however, detailed...
Abstract Elevated levels of uric acid, a metabolite purine in humans, is related to various diseases, such as gout, atherosclerosis and renal dysfunction. The excretion reabsorption acid to/from urine tightly regulated by transporters. amino sequences transporters, URAT1/ SLC22A12 , OAT4/ SLC22A11 OAT10/ SLC22A13 share closer phylogenic relationship, whereas the gene promoter are distant relationship. Through single-cell RNA-sequencing analysis an adult human kidney, we found that only small...
Summary The brainstem controls heartbeat, blood pressure and respiration, which are life-sustaining functions, therefore, disorders of the can be lethal. Brain organoids derived from human pluripotent stem cells recapitulate course brain development expected to useful for medical research on central nervous system disorders. However, existing organoid models have limitations, hampering elucidation diseases affecting specific components brain. Here, we developed a method generate (hBSOs),...
Abstract Amyotrophic lateral sclerosis (ALS) is an irreversible neurodegenerative disease caused by the degeneration of motor neurons, and cytoskeletal instability considered to be involved in neurodegeneration. A hexanucleotide repeat expansion C9orf72 , one most common causes familial ALS, produces toxic proline:arginine (PR) poly-dipeptides. PR poly-dipeptides binds polymeric forms low complexity sequences intracellular puncta, thereby altering intermediate filaments (IFs). However, how...
Abstract In humans, uric acid is an end-product of purine metabolism. Urate excretion from human kidney tightly regulated by reabsorption and secretion. At least eleven genes have been identified as renal urate transporters. However, it remains unclear whether all tubular cells express the same set Here we show that are divided into three distinct cell populations for handling. Analysis healthy kidneys at single-cell resolution revealed not expressed Only 32% were related to both secretion,...
Abstract Chronic kidney disease (CKD) is a progressive disease, and podocyte injury potential mechanism. We found that Matriptase was activated at podocytes in CKD patients mice while inhibitor slowed the progression of mouse disease. The mechanism could be accounted for by an imbalance favoring over its cognate inhibitor, hepatocyte growth factor activator type 1 (HAI-1), as conditional depletion HAI-1 accelerates injury. Intriguingly, N-terminal Podocin (Podocin-N), consequence cleavage...
ABSTRACT The anticancer agent, 5-fluorouracil (5-FU), is typically applied in the treatment of various types cancers because its properties. Thought to be an inhibitor enzyme thymidylate synthase which plays a role nucleotide synthesis, 5-FU has been found induce single- and double-strand DNA breaks. activation ATR occurs as reaction UV- chemotherapeutic drug-induced replication stress. In this study, we examined effect inhibition on sensitivity. Using western blotting, that led...
Abstract Reverse transcription quantitative PCR (RT-qPCR) is used to quantify gene expression and require standardization with reference genes. We sought identify the genes best suited for experiments that induce osteogenic differentiation from human induced pluripotent stem (iPS) cells. They were cultured in an undifferentiated maintenance medium after confluence, further 28 days. RT-qPCR was performed on undifferentiation markers, osteoblast osteocyte candidates. The stability of each...