- TGF-β signaling in diseases
- Angiogenesis and VEGF in Cancer
- Atherosclerosis and Cardiovascular Diseases
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Regulation of Appetite and Obesity
- Connective Tissue Growth Factor Research
- Cancer-related gene regulation
- Cancer, Hypoxia, and Metabolism
- Helicobacter pylori-related gastroenterology studies
- RNA Research and Splicing
- Bone Metabolism and Diseases
- Glycosylation and Glycoproteins Research
- Kruppel-like factors research
- Biochemical Analysis and Sensing Techniques
- Pulmonary Hypertension Research and Treatments
- Axon Guidance and Neuronal Signaling
- Adipose Tissue and Metabolism
- Chemokine receptors and signaling
- Bone and Dental Protein Studies
- Galectins and Cancer Biology
- Retinoids in leukemia and cellular processes
- Congenital heart defects research
- Carbohydrate Chemistry and Synthesis
- Cytokine Signaling Pathways and Interactions
- Infant Health and Development
Kobe Pharmaceutical University
2021-2025
Nippon Medical School
2015-2025
Josai University
2006-2024
Kyoto first Red Cross hospital
2022-2024
Nippon Medical School Hospital
2022-2024
Tosoh (Japan)
2023
Keio University
2006-2022
National Cerebral and Cardiovascular Center
2015-2021
Osaka University
2004-2020
Osaka University of Pharmaceutical Sciences
2017-2018
Vascular calcification is prevalent in patients with diabetes and chronic kidney disease. Receptor for advanced glycation end products (RAGE) its multiple ligands have been implicated the pathogenesis of accelerated atherosclerosis; however, little known about effects RAGE activation on vascular calcification.Cultured rat human aortic smooth muscle cells (HASMC) were transduced adenovirus expressing RAGE. Expression myocardin SMC-marker genes was significantly repressed these cells....
Although aberrant proliferation and activation of lung fibroblasts are implicated in the initiation progression idiopathic pulmonary fibrosis (IPF), underlying mechanisms not well characterized. Numerous microRNAs (miRNAs) have been this process; however, miRNAs derived from exosomes relevance such to fibroblast-to-myofibroblast differentiation understood. In study, we attempted identify exosome-derived relevant development.Using miRNA array analysis, profiled expression sera C57BL/6 mice...
Rho-associated coiled-coil protein kinase (ROCK) is an effector for the small GTPase Rho and plays a pivotal role in diverse cellular activities, including cell adhesion, cytokinesis, gene expression, primarily through alteration of actin cytoskeleton dynamics. Here, we show that ROCK2 localized nucleus associates with p300 acetyltransferase both vitro cells. Nuclear present large complex partially cofractionates by gel filtration analysis. By immunofluorescence, colocalizes distinct...
Myocardin is a coactivator of serum response factor (SRF) required for vascular smooth muscle cell (VSMC) differentiation. HERP1 transcriptional repressor, which abundantly expressed in system and known to function as target gene Notch. However, the role pathogenesis lesions remains unknown. The present study characterizes expression normal diseased vessels, tests hypothesis that inhibits SRF/myocardin-dependent SMC expression.Immunohistochemistry revealed myocardin was localized neointima...
BackgroundIngestion of the lectins present in certain improperly cooked vegetables can result acute GI tract distress, but mechanism toxicity is unknown. In vivo, gut epithelial cells are constantly exposed to mechanical and other stresses consequently individual frequently experience plasma membrane disruptions. Repair these cell surface disruptions allows wounded survive: failure results necrotic death. Plasma repair mediated, part, by an exocytotic event that adds a patch internal defect...
Vascular calcification is regulated in a process similar to bone formation. BMP2 (bone morphogenetic protein 2) essential for osteoblastic differentiation of mesenchymal progenitor cells and thus has been implicated the development vascular calcification. Here we examined whether Notch signaling interacts with regulate osteogenic mineralization smooth muscle (SMCs). alone scarcely induced expression alkaline phosphatase (ALP), an ectoenzyme crucially required active biomineralization, human...
β-catenin regulates the transcription of genes involved in diverse biological processes, including embryogenesis, tissue homeostasis and regeneration. Endothelial cell (EC)-specific gene-targeting analyses mice have revealed that is required for vascular development. However, precise function β-catenin-mediated gene regulation development not well understood, since only expression but also formation cell-cell junctions. To address this question, we developed a novel transgenic zebrafish line...
The undifferentiated state of muscle stem (satellite) cells (MuSCs) is maintained by the canonical Notch pathway. Although three bHLH transcriptional factors, Hey1, HeyL and Hes1, are considered to be potential effectors pathway exerting anti-myogenic effects, neither nor Hes1 inhibits myogenic differentiation cell lines. Furthermore, whether these factors work redundantly or cooperatively unknown. Here, we showed cell-autonomous functions Hey1 in MuSCs using conditional genetic null mice....
Intracranial aneurysms (IAs) are a high-risk factor for life-threatening subarachnoid hemorrhage. Their etiology, however, remains mostly unknown at present. We conducted screening sporadic somatic mutations in 65 IA tissues (54 saccular and 11 fusiform aneurysms) paired blood samples by whole-exome targeted deep sequencing. identified multiple signaling genes examined their impact on downstream pathways gene expression vitro an arterial dilatation model mice vivo. 16 that were mutated least...
Dimethylarginie dimethylaminohydrolase (DDAH) is a degrading enzyme for asymmetrical dimethylarginine, an endogenous NO synthase inhibitor. The molecular mechanism DDAH-induced vascular endothelial growth factor (VEGF) expression was examined.Although the transfection of vectors 2 isoforms DDAH, DDAH1, or DDAH2 increased DDAH activity in bovine aortic cells and human umbilical vein cells, secretion VEGF were only DDAH2-transfected cells. Knocking down gene reduced production, overexpression...
Phenotypic plasticity and the switching of vascular smooth muscle cells (SMCs) play a critical role in atherosclerosis. Although Runx2, key osteogenic transcription factor, is expressed atherosclerotic plaques, molecular mechanisms by which Runx2 regulates SMC differentiation remain unclear. Here we demonstrated that repressed induced myocardin, acts as coactivator for serum response factor (SRF). Myocardin-mediated induction gene expression was enhanced mouse embryonic fibroblasts derived...
Vascular calcification is closely correlated with cardiovascular morbidity and mortality. Here, we demonstrate the role of Notch signaling in osteogenic differentiation mineralization vascular smooth muscle cells (SMCs).The Msx2 gene, a key regulator osteogenesis, was highly induced by coculture ligand-expressing or overexpression intracellular domains (NICDs) human aortic SMCs (HASMCs). Furthermore, Notch1 domain (N1-ICD) markedly upregulated alkaline phosphatase (ALP) activity matrix...
The upper gastrointestinal (GI) tract undergoes a temporally coordinated cyclic motor pattern known as the migrating complex (MMC) in both dogs and humans during fasted state. Feeding results replacement of MMC by noncyclic, intermittent contractile activity termed postprandial contractions. Although is to be stimulated motilin, recent studies have shown that ghrelin, which from same peptide family also involved regulation MMC. In present study, we investigated role vagus nerve on gastric...
Ultraviolet B (UV-B) irradiation is an effective treatment for human cutaneous disorders and was shown to reduce experimental atherosclerosis by attenuating immunoinflammatory responses. The aim of this study clarify the effect specific wavelengths UV-B on underlying mechanisms focusing
Chronic inflammation via dysregulation of T cell immune responses is critically involved in the pathogenesis atherosclerotic cardiovascular disease. Improving balance between proinflammatory cells and anti-inflammatory regulatory (Tregs) may be an attractive approach for treating atherosclerosis. Although C-C chemokine receptor 4 (CCR4) has been shown to mediate recruitment inflamed tissues, its role atherosclerosis unclear. Here, we show that genetic deletion CCR4 hypercholesterolemic mice...
Our previous studies identified ultraviolet B (UVB) irradiation as a possible approach for preventing atherosclerosis. The aim of this study was to clarify the effect 312 nm UVB, wavelength similar that clinically available narrow-band UVB treatment psoriasis, on atherosclerosis and underlying mechanisms. Using recently developed UVB-light-emitting diode device, we irradiated 6-week-old male atherosclerosis-prone apolipoprotein E-deficient mice with at 5 or 10 kJ/m² examined its development...
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare complication during dupilumab therapy. However, the optimal treatment strategy for dupilumab-triggered EGPA remains unclear, particularly timing and role of anti-interleukin-5 A 48-year-old female severe eosinophilic rhinosinusitis asthma, increased blood eosinophils (2098/μL) myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA) (46.1 U/mL) without vasculitic symptoms, developed systemic including fever,...
Abstract —Transforming growth factor (TGF)-β plays a major role in the development of vascular diseases. Despite pleiotropic effects TGF-β on smooth muscle cells (VSMCs), only few genes have been characterized as direct targets VSMCs. Cardiac ankyrin repeat protein (CARP) has thought to be expressed exclusively heart. In present study, we showed that CARP is vasculature after balloon injury and cultured VSMCs response TGF-β. Analysis half-life cytoplasmic mRNA levels transient transfection...
Ghrelin, an endogenous ligand for the GH secretagogue receptor, is predominantly produced in stomach. Little known about regulation mechanism of gastric ghrelin. Here, we report that estrogen synthesized stomach induces rat ghrelin gene expression and production. We established a cell enrichment method using Percoll centrifugation then studied effect and/or its antagonist on Treatment with 8 h significantly increased level expression, ICI-182 780, receptor (ER) antagonist, completely...
Objective— TGFβ and proliferation/phenotypic switching of smooth muscle cells (SMCs) play a pivotal role in pathogenesis atherosclerotic restenotic lesions after angioplasty. We have previously shown that the protein inhibitor activated STAT (PIAS)1 activates expression SMC differentiation marker genes including (SM) α-actin by interacting with serum response factor (SRF) class I bHLH proteins. Here, we tested hypothesis SM through PIAS1. Methods Results— An siRNA specific for PIAS1 ubc9, an...