A5101760863- TGF-β signaling in diseases
- Endoplasmic Reticulum Stress and Disease
- Ion Channels and Receptors
- NF-κB Signaling Pathways
- Cancer-related gene regulation
- Genetic factors in colorectal cancer
- Renal and related cancers
- Autophagy in Disease and Therapy
- Rheumatoid Arthritis Research and Therapies
- Neurobiology and Insect Physiology Research
- Biochemical Analysis and Sensing Techniques
- Epigenetics and DNA Methylation
- Cytokine Signaling Pathways and Interactions
- Toxin Mechanisms and Immunotoxins
- Systemic Lupus Erythematosus Research
- Cancer-related Molecular Pathways
- Hedgehog Signaling Pathway Studies
- Histone Deacetylase Inhibitors Research
- Calcium signaling and nucleotide metabolism
- Forensic Toxicology and Drug Analysis
- FOXO transcription factor regulation
- Wnt/β-catenin signaling in development and cancer
- Plant Disease Management Techniques
- Advanced MRI Techniques and Applications
- Bioactive natural compounds
University of Yamanashi
2018-2025
Science for Life Laboratory
2025
Uppsala University
2025
Nagoya City University
2011-2021
University of Yamanashi Hospital
2017
Showa University
2014
Aichi Gakuin University
2008-2013
National Defense Medical College
2005
Abstract Transforming growth factor β (TGF-β) signaling facilitates tumor development during the advanced stages of tumorigenesis, but induces cell-cycle arrest for suppression early stages. However, mechanism functional switching TGF-β is still unknown, and it unclear whether inhibition results amelioration or exacerbation cancers. Here we show that suppressor p53 cooperates with Smad proteins, which are signal transducers, to selectively activate plasminogen activator inhibitor type-1...
The p53 tumor suppressor plays critical roles in cell cycle regulation and apoptotic death response to various cellular stresses, thereby preventing cancer development. Therefore, the activation of through small molecules is an attractive therapeutic strategy for treatment cancers retaining wild-type p53. We used a library 700 Myanmar wild plant extracts identify that induce transcriptional activity. A cell-based screening method with p53-responsive luciferase-reporter assay system revealed...
ABSTRACT Snail is a zinc finger transcription factor encoded by the SNAI1 gene and triggers cellular process termed epithelial‐mesenchymal transition (EMT) upon its increased expression and/or functional activation. activity are regulated various extracellular stimuli, including cytokines environmental factors. Transforming growth factor‐β (TGF‐β) inducer that functions via Smad3‐mediated transcriptional In present study, we identified distal enhancer modulates TGF‐β–induced expression....
Abstract Rheumatoid arthritis (RA) occurs four times more frequently in women than men, although the mechanistic basis of gender difference is unknown. RA characterized by overproliferation synoviocytes producing proinflammatory cytokines such as IL-1, implicated pathogenesis disease. In this study we examined whether 17β-estradiol (E2) induced IL-1α mRNA expression rheumatoid fibroblast-like cell line MH7A, well primary synovial cells from patients, and investigated underlying molecular...
The activation of a vanilloid type 4 transient receptor potential channel (TRPV4) has an obligatory role in regulation intracellular Ca(2+) (Ca(2+)(i)) several types cells including vascular and sensory organs. In this study, we provide evidence that TRPV4 is functional regulator Ca(2+)(i) human synoviocytes. Although significant expression synoviocytes from patients with (RA) without (CTR) rheumatoid arthritis was detected at mRNA protein level, those the fibroblast-like synoviocyte line...
Smad proteins are transcriptional regulators activated by TGF-β. They known to bind two distinct Smad-responsive motifs, namely the Smad-binding element (SBE) (5'-GTCTAGAC-3') and CAGA motifs (5'-AGCCAGACA-3' or 5'-TGTCTGGCT-3'). However, mechanisms which these promote activity not fully elucidated. In this study, we performed DNA CASTing, binding assays, ChIP sequencing, quantitative RT-PCR dissect details of function SBE motifs. We observed a preference for Smad3 Smad4 SBE, that either one...
Rheumatoid arthritis (RA) is characterized by proliferation of synoviocytes that produce proinflammatory cytokines, which are implicated in the pathogenesis RA. When human fibroblast-like line MH7A was treated with cigarette smoke condensate (CSC), either mainstream or sidestream, expression levels interleukin (IL)-1α, IL-1β, IL-6, IL-8, and CYP1A1 mRNA were upregulated both time- dose-dependent manners. The upregulatory effects CSC on these cytokines not significantly inhibited...
The epithelial–mesenchymal transition (EMT) is a crucial morphological event that occurs during epithelial tumor progression. Snail and ZEB1/2 (ZEB1 ZEB2), known as EMT transcription factors, are key regulators of this transition. positively correlated with phenotypes the aggressiveness cancers. On contrary, also cancers, but not expression marker proteins. induced by transforming growth factor‐β (TGF‐β), well‐known inducer EMT, in various cancer cells. Interestingly, induction TGF‐β...
Rheumatoid arthritis (RA) is a disease with significant gender differences in its prevalence and clinical features. Interleukin (IL)-1 tumor necrosis factor (TNF) α produced by synoviocytes are principle inflammatory destructive mediators of RA. We found that potent androgen, 5α-dihydrotestosterone (DHT) inhibits IL-1α-induced production mRNA expression IL-8, IL-6 IL-1β from RA patient-derived fibroblast-like synovial cell line MH7A. Promoter analysis the IL-8 gene revealed nuclear (NF)-κB...
Transient receptor potential ankyrin 1 (TRPA1) is a Ca(2+)-permeable nonselective cation channel expressed in neuronal and nonneuronal cells plays an important role acute inflammatory pain. Here, we show that NADPH oxidase (NOX) inhibitor, diphenyleneiodonium (DPI), functions as TRPA1 activator human embryonic kidney expressing (HEK-TRPA1) fibroblast-like synoviocytes. Application of DPI at 0.03-10 μM induced Ca(2+) response HEK-TRPA1 concentration-dependent manner. The was effectively...
Abstract Transforming growth factor‐β (TGF‐β) is a pleiotropic cytokine that modulates wide variety of cellular responses by regulating target gene expression. It principally transmits signals via receptor‐activated transcription factors Smad2 and Smad3, which form trimeric complexes with Smad4 upon activation regulate expression binding to genomic DNA. Here, we examined the mechanisms TGF‐β regulates genes in cell context‐dependent manner screening double‐stranded DNA oligonucleotide...
Tribbles 1 (TRB1), a member of the family, is pseudokinase that conserved among species and implicated in various human diseases including leukemia, cardiovascular diseases, metabolic disorders. However, role TRB1 immune response not understood. To evaluate this role, we examined regulation expression function interleukin-2 (IL-2) induction Jurkat cells, acute T cell leukemia line. We found was strongly induced by phorbol 12-myristate 13-acetate (PMA) ionomycin these cells. IL-2 cells...