A5048410124- Neonatal Respiratory Health Research
- TGF-β signaling in diseases
- Congenital heart defects research
- Bone Metabolism and Diseases
- T-cell and B-cell Immunology
- Heart Failure Treatment and Management
- Muscle Physiology and Disorders
- Medical Imaging and Pathology Studies
- Pulmonary Hypertension Research and Treatments
- GDF15 and Related Biomarkers
- Immune Cell Function and Interaction
- Acute Kidney Injury Research
- Wnt/β-catenin signaling in development and cancer
- Spaceflight effects on biology
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Ion Transport and Channel Regulation
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Sarcoma Diagnosis and Treatment
- Chemokine receptors and signaling
- Autophagy in Disease and Therapy
- Asthma and respiratory diseases
- Cardiac Fibrosis and Remodeling
- Protein Tyrosine Phosphatases
- Coronary Artery Anomalies
- Cancer Mechanisms and Therapy
Nippon Medical School
2023-2025
National Cerebral and Cardiovascular Center
2016-2022
Chiba University
2008-2018
Chiba University Hospital
2009-2016
Japan Society for the Promotion of Science
2014-2015
Japan Science and Technology Agency
2010
Abstract Introduction It is not well understood whether the process of autophagy accelerated or blocked in sepsis, and it beneficial harmful to immune defense mechanism over a time course during sepsis. Our aim was determine both kinetics role Methods We examined autophagosome autolysosome formation cecal ligation puncture (CLP) mouse model sepsis (in C57BL/6N mice GFP-LC3 transgenic mice), using western blotting, immunofluorescence, electron microscopy. also investigated effect chloroquine...
Despite widespread adoption of tissue clearing techniques in recent years, poor access to suitable light-sheet fluorescence microscopes remains a major obstacle for biomedical end-users. Here, we present descSPIM (desktop-equipped SPIM cleared specimens), low-cost ($20,000-50,000), low-expertise (one-day installation by non-expert), yet practical do-it-yourself microscope as solution this bottleneck. Even the most fundamental configuration enables multi-color imaging whole mouse brains and...
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....
Insulin-like growth factor 1 (IGF-1) induces skeletal muscle maturation and enlargement (hypertrophy). These responses require protein synthesis myofibril formation (myofibrillogenesis). However, the signaling mechanisms of myofibrillogenesis remain obscure. We found that IGF-1-induced phosphatidylinositol 3-kinase-Akt formed a complex nebulin N-WASP at Z bands myofibrils by interfering with glycogen synthase kinase-3β in mice. Although is known to be an activator Arp2/3 form branched actin...
Although peptides are safe and useful as therapeutics, they often easily degraded or metabolized. Dampening the clearance system for peptide ligands is a promising strategy increasing efficacy of therapies. Natriuretic receptor B (NPR-B) its naturally occurring ligand, C-type natriuretic (CNP), potent stimulators endochondral bone growth, activating CNP/NPR-B expected to be powerful treating impaired skeletal growth. CNP cleared by (NPR-C); therefore, we investigated effect reducing rate on...
Abstract Alveologenesis is a spatially coordinated morphogenetic event, during which alveolar myofibroblasts surround the terminal sacs constructed by epithelial cells and endothelial (ECs), then contract to form secondary septa generate alveoli in lungs. Recent studies have demonstrated important role of ECs this event. However, mechanisms underlying EC-mediated alveologenesis remain unknown. Herein, we show that regulate constructing basement membranes (BMs) acting as scaffold for induce...
Keloids are a complex type of scar tissue formed by exaggerated wound healing, characterised the overgrowth thick fibrous beyond original boundary. While crucial relationship between keloid formation and vascular system has been highlighted, conflicting findings have reported regarding characterisation vasculature. Here, we successfully detailed three-dimensional (3D) structure vasculature in tissues using clearing methods combined with 3D imaging. First, compared two optical methods, clear,...
The small GTPase RhoD regulates actin cytoskeleton to collapse stress fibers and focal adhesions, resulting in suppression of cell migration cytokinesis. It also induces alignment early endosomes along filaments reduces their motility. We show here that a constitutively activated generated two types actin-containing thin peripheral cellular protrusions distinct from Cdc42-induced filopodia. One was longer, almost straight, immotile, sensitive fixation, whereas the other shorter, undulating,...
Myofibroblasts play critical roles in the development of idiopathic pulmonary fibrosis by depositing components extracellular matrix. One source lung myofibroblasts is thought to be alveolar epithelial type 2 cells that undergo epithelial–mesenchymal transition (EMT). Rat RLE-6TN treated with transforming growth factor-β1 (TGF-β1) are converted into through EMT. TGF-β induces both canonical Smad signaling and non-canonical signaling, including Ras-induced ERK pathway (Raf–MEK–ERK). However,...
The heart is an endocrine organ, as cardiomyocytes (CMs) secrete natriuretic peptide (NP) hormones. Since the discovery of NPs, no other hormones that affect remote organs have been identified from heart. We osteocrin (Ostn) osteogenesis/chondrogenesis regulatory hormone secreted CMs in zebrafish. ostn mutant larvae exhibit impaired membranous and chondral bone formation. bones were recovered by CM-specific overexpression OSTN. analyzed parasphenoid (ps) a representative bones. In shortened...
CXCR4 expression is critical for localization of centroblasts in the dark zone germinal centers (GCs), and centrocytes downregulate thus leave to reside light zone. However, mechanisms governing downregulation on are not known. In this study, we show that amount intracellular was similar centrocytes, suggesting differential control protein these GC B cells. Restimulation activated cells with IL-21, which a major cytokine produced by T follicular helper cells, accelerated internalization...
Significance Alveoli participating in gas exchange are essential for maintaining life air-breathing vertebrates. In developing lungs, alveolar myofibroblasts (AMYFs) cause morphological changes of interalveolar walls and consequently generate alveoli. Although the Ras-ERK signaling pathway is known to regulate formation, molecular cellular mechanisms underlying its role remain largely obscure. Here, we clarified a critical DA-Raf1 (DA-Raf)—a dominant-negative antagonist pathway—in formation....
Significance It has been suggested that the transcriptional repressor Bcl6 suppresses T helper 2 (T H 2) immune responses underlying allergic diseases. However, molecular role of B-cell CLL/lymphoma 6 (Bcl6) in cells is incompletely understood pathophysiological settings. We found suppressed cytokine production memory through binding to intron Interkeukin 4 ( Il4 ) locus using murine models. Furthermore, IL-33 controlled function at chromatin level and consequently, augmented cells....
Abstract The Nczf gene has been identified as one of Ncx target genes and encodes a novel KRAB zinc-finger protein, which functions sequence specific transcriptional repressor. In order to elucidate functions, we generated knockout (Nczf−/−) mice. Nczf−/− mice died around embryonic day 8.5 (E8.5) with small body size impairment axial rotation. Histopathological analysis revealed that the cell number decreased pyknotic cells were occasionally observed. We examined expression cycle related in...
Abstract Natriuretic peptides exert multiple effects by binding to natriuretic peptide receptors (NPRs). Osteocrin (OSTN) binds with high affinity NPR-C, a clearance receptor for peptides, and inhibits degradation of consequently enhances guanylyl cyclase-A (GC-A/NPR1) signaling. However, the roles OSTN in kidney have not been well clarified. Adriamycin (ADR) nephropathy wild-type mice showed albuminuria, glomerular basement membrane changes, increased podocyte injuries, infiltration...
Abstract Vascular permeability is dynamically but tightly controlled by vascular endothelial (VE)‐cadherin‐mediated cell–cell junctions to maintain homeostasis. Thus, impairments of VE‐cadherin‐mediated cell adhesions lead hyperpermeability, promoting the development and progression various disease processes. Notably, lungs are a highly vulnerable organ wherein pulmonary inflammation infection result in leakage. Herein, we showed that Rap1, small GTPase, plays an essential role for...
Background Polymorphisms of the Plant homeodomain finger protein 11 (PHF11) are strongly associated with high serum IgE levels and clinical severity atopic patients. However, precise mechanism has not been fully elucidated. We investigated role Phf11 in class switch recombination (CSR) to by activated B cells. Methods generated transgenic (Lckd-Phf11-Tg) mice that express exogenous murine lymphocytes under control distal Lck promoter. examined IL-4-induced CSR Lckd-Phf11-Tg cells vitro....
Transcriptional repressor B-cell lymphoma 6 (Bcl6) appears to regulate TH2 immune responses in allergies, but its precise role is unclear. We previously reported that Bcl6 suppressed IL-4 production naïve CD4+ T cell-derived memory cells. To investigate function allergic naturally occurring phenotype (MPT) cells and their derived (MPTH2) cells, Bcl6-manipulated mice, highly conserved intron enhancer (hcIE)-deficient reporter mice for noncoding sequence 2 (CNS2) 3′ distal region were used...