A5066018988- Cellular Mechanics and Interactions
- Cell Adhesion Molecules Research
- Cardiac Valve Diseases and Treatments
- Aortic Disease and Treatment Approaches
- Cardiac Structural Anomalies and Repair
- Aortic aneurysm repair treatments
- Cardiac and Coronary Surgery Techniques
- Infectious Aortic and Vascular Conditions
- 3D Printing in Biomedical Research
- Bone Metabolism and Diseases
- Cardiac, Anesthesia and Surgical Outcomes
- Exercise and Physiological Responses
- Neurogenesis and neuroplasticity mechanisms
- Infective Endocarditis Diagnosis and Management
- Muscle Physiology and Disorders
- Heart Rate Variability and Autonomic Control
- Force Microscopy Techniques and Applications
- Botulinum Toxin and Related Neurological Disorders
- Neurogenetic and Muscular Disorders Research
- Spaceflight effects on biology
- NF-κB Signaling Pathways
- Congenital Heart Disease Studies
- Tendon Structure and Treatment
- Functional Brain Connectivity Studies
- Skin and Cellular Biology Research
National Rehabilitation Center for Persons with Disabilities
2015-2023
National Cerebral and Cardiovascular Center
2020-2023
The University of Tokyo
2000-2020
Tokyo University of Agriculture and Technology
2020
Mie Chuo Medical Center
2019-2020
Anjo Kosei Hospital
2012-2019
National University of Singapore
2012-2019
Nadogaya Hospital
2012-2019
Yamaguchi Prefectural University
2016
Yamaguchi University
2016
To examine the role of mitogen-activated protein kinase and nuclear factor kappa B (NF-κB) pathways on osteoclast survival activation, we constructed adenovirus vectors carrying various mutants signaling molecules: dominant negative Ras (RasDN), constitutively active MEK1 (MEKCA), IκB 2 (IKKDN), IKK2 (IKKCA). Inhibiting ERK activity by RasDN overexpression rapidly induced apoptosis osteoclast-like cells (OCLs) formed in vitro, whereas activation after introduction MEKCA remarkably lengthened...
Force-initiated signal transduction can occur either via membrane-based ionic mechanisms or through changes in cytoskeletal–matrix linkages. We report here the stretch-dependent binding of cytoplasmic proteins to Triton X-100 cytoskeletons L-929 cells grown on collagen-coated silicone. X-100–insoluble were stretched by 10% and incubated with biotinylated proteins. Analysis two-dimensional gel electrophoresis showed more than 10 protein spots. Bound purified a photocleavable biotin tag...
Abstract Multipotent neural precursor cells (NPCs) generate astrocytes at late stages of mammalian neocortical development. Many signalling pathways that regulate astrocytogenesis directly induce the expression GFAP, a marker terminally differentiated astrocytes. However, astrocyte specification occurs before GFAP and essential factors for step have remained elusive. Here we show Zbtb20 regulates in mouse neocortex. is highly expressed late-stage NPCs their astrocytic progeny. Overexpression...
Caloric restriction (CR) is known to retard aging and delay functional decline as well the onset of diseases in most organisms. Ghrelin secreted from stomach response CR regulates energy metabolism. We hypothesized that ghrelin has a role protecting aging-related diseases. examined physiological mechanisms underlying system during process three mouse strains with different genetic biochemical backgrounds animal models accelerated or normal human aging. The elevated plasma concentration was...
Mechanical stimuli including loading after birth promote bone growth. However, little is known about how mechanical force triggers biochemical signals to regulate Here, we identified a periosteal-osteoblast-derived secretory peptide, Osteocrin (OSTN), as mechanotransducer involved in load-induced long OSTN produced by periosteal osteoblasts regulates growth plate enhancing C-type natriuretic peptide (CNP)-dependent proliferation and maturation of chondrocytes, leading elongation bones....
Cells differentiate in response to various extracellular stimuli. This cellular requires intracellular signaling pathways. The mitogen-activated protein (MAP) kinase cascade is a core signal transduction pathway that determines the fate of many kinds cell. MAP activates kinase, which turn kinase. Apoptosis signal-regulating (ASK1) was identified as involved stress-induced apoptosis-signaling SEK1-JNK and MKK3/MKK6-p38 cascades. Expression constitutively active form ASK1 (ASK1-ΔN)...
ABSTRACT Mechanical force or mechanical stress modulates intracellular signal pathways, including the mitogen-activated protein kinase (MAP kinase) cascades. In our system, cell stretching activated and contraction inactivated all three MAP pathways (MKK1/2-extracellular signal-regulated (ERK), MKK4 (SEK1)-cJun N-terminal (JNK) MKK3/6-p38 pathways). However, little is known about molecular mechanisms that link to To test whether Ras Rap1 are possible components in stretch-activated we...
IL-12 is a 70-kDa heterodimeric cytokine composed of two covalently linked chains, p40 and p35. has multiple effects on T NK cells recently was found to be required for optimal Th1 cell development. In variety inflammatory skin disorders including delayed type hypersensitivity contact hypersensitivity, appear critically involved. Because keratinocytes are well known exhibit the capacity release proinflammatory immunologic cytokines, thereby able modulate immune reactions within skin, it...
Recent studies reveal that the mechanical environment influences behavior and function of various types cells, including stem cells. However, signaling pathways involved in regulation cell properties remain largely unknown. Using polyacrylamide gels with varying Young's moduli as substrates, we demonstrate mouse embryonic cells (mESCs) are induced to differentiate on substrates defined elasticity, involving Src-ShcA-MAP kinase pathway. While dual inhibition mitogen-activated protein (MAP)...
Oncogenic Ras induces cell transformation and promotes an invasive phenotype. The tumor suppressor p53 has a suppressive role in Ras-driven invasion. However, its mechanism remains poorly understood. Here we show that activation of the mitochondrial protease high-temperature requirement A2 (HtrA2; also known as Omi) prevents invasion by modulating actin cytoskeleton. increases accumulation cytoplasm, which translocation p38 mitogen-activated protein kinase (MAPK) into mitochondria...
Oligodendrocyte progenitor cells (OPCs) undergo marked morphological changes to become mature oligodendrocytes, but the metabolic resources for this process have not been fully elucidated. Although lactate, a derivative of glycogen, has reported be consumed in oligodendrocytes as metabolite, and ameliorate hypomyelination induced by low glucose conditions, it is clear about direct contribution lactate cell cycling differentiation OPCs, source remyelination. Therefore, we evaluated effect...
We describe the design and validation of an equibiaxial stretching device in which cells are confined to regions homogeneous strain. Using this device, we seek overcome a significant limitation existing devices, strains not over entire region cell culture. cast PDMS mold produce membrane with cylindrical wall incorporated center, was used confine monolayers central subjected demonstrated that presence hold culture medium did affect strain homogeneity majority surface also showed adhered well...
Mechanical loading plays an important role in bone homeostasis. However, molecular mechanisms behind the mechanical regulation of homeostasis are poorly understood. We previously reported p130Cas (Cas) as a key molecule cellular mechanosensing at focal adhesions. Here, we demonstrate that Cas is distributed nucleus and supports loading-mediated by alleviating NF-κB activity, which would otherwise prompt inflammatory processes. unloading modulates distribution activity osteocytes,...
The serum phosphorylated neurofilament heavy subunit (pNF-H) is a nervous system-specific protein that released from damaged neural tissue after traumatic brain injury (TBI). aim of this study was to elucidate the usefulness pNF-H as predictive marker for outcome patients TBI. Patients with TBI (Glasgow Coma Scale score 13 or less on admission) were included. who younger than age 18, dependent others daily activities before injury, pregnant, not likely survive more 24 h excluded. assessed...
Oligodendrocyte precursor cells (OPCs) act as a reservoir of new oligodendrocytes (OLs) in homeostatic and pathological conditions. OPCs are activated response to injury generate myelinating OLs, but the underlying mechanisms remain poorly understood. Here, we show that chromodomain helicase DNA binding protein 7 (Chd7) regulates OPC activation after spinal cord (SCI). Chd7 is expressed adult its expression upregulated with concomitant increase Sox2 SCI. OPC-specific ablation injured mice...
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease that associated with persistent inflammation and extracellular matrix degradation. The molecular mechanisms underlying the macrophage-mediated progression of AAA remain largely unclear.We show focal adhesion kinase (FAK) expression activity are enhanced in macrophages recruited to tissue. FAK potentiates tumor necrosis factor-α-induced secretion matrix-degrading enzymes chemokines by cultured macrophages. also promotes...
Tumor suppressor p53 prevents tumorigenesis and tumor growth by suppressing the activation of several transcription factors, including nuclear factor-κB (NF-κB) STAT3. On other hand, stimulates actin cytoskeleton remodeling integrin-related signaling cascades. Here, we examined p53-mediated link between regulation NF-κB STAT3 in MCF-7 cells mouse embryonic fibroblasts (MEFs). In absence p53, was constitutively activated. This attenuated depleting expression p65, a component NF-κB. Integrin...
Anchorage-independent growth is the most significant hallmark of cell transformation, which has an intimate relevance to cancer. Anchorage or adhesion physically links cells extracellular matrix and allows transmission external mechanical cues intracellular signaling machineries. Transformation involves acquiring ability proliferate without requiring mechanically initiated signal transduction, known as mechanotransduction. A number cytoskeletal molecules are located at focal adhesions. Src...
The physical properties of the extracellular matrix (ECM), such as stiffness, are involved in determination characteristics cancer cells, including chemotherapy sensitivity. Resistance to is often linked dysfunction tumor suppressor p53; however, it remains elusive whether ECM microenvironment interferes with p53 activation cells. Here, we show that, MCF-7 breast stiffness influences induced by antitumor drug doxorubicin. Cell growth inhibition doxorubicin was increased response rigidity a...
Abstract The mechanisms by which physical exercise benefits brain functions are not fully understood. Here, we show that vertically oscillating head motions mimicking mechanical accelerations experienced during fast walking, light jogging or treadmill running at a moderate velocity reduce the blood pressure of rats and human adults with hypertension. In hypertensive rats, shear stresses less than 1 Pa resulting from interstitial-fluid flow induced such passive reduced expression angiotensin...