A5055425111- Protein Kinase Regulation and GTPase Signaling
- Hippo pathway signaling and YAP/TAZ
- Adipose Tissue and Metabolism
- Axon Guidance and Neuronal Signaling
- Microtubule and mitosis dynamics
- Signaling Pathways in Disease
- Cardiac Fibrosis and Remodeling
- Kruppel-like factors research
- Extracellular vesicles in disease
- Cellular Mechanics and Interactions
- Mesenchymal stem cell research
- Cardiovascular Function and Risk Factors
- TGF-β signaling in diseases
- Cancer, Hypoxia, and Metabolism
- Amino Acid Enzymes and Metabolism
- Cardiomyopathy and Myosin Studies
- Circadian rhythm and melatonin
- Stress Responses and Cortisol
- Fibroblast Growth Factor Research
- Bone Metabolism and Diseases
- Cardiac electrophysiology and arrhythmias
- Cellular transport and secretion
- Mechanisms of cancer metastasis
- Angiogenesis and VEGF in Cancer
- Neurogenesis and neuroplasticity mechanisms
Nagoya University
2013-2025
University of Münster
2015-2022
Max Planck Institute for Molecular Biomedicine
2015-2022
Nagoya University Hospital
2020
Morpho (United States)
2015
Tosei General Hospital
2013
Nagoya City University
2011
Nihon University
2006
Nippon Steel (Japan)
1988
Meiji University
1970
Angiogenic blood vessel growth requires several distinct but integrated cellular activities. Endothelial cell sprouting and proliferation lead to the expansion of vasculature give rise a highly branched, immature plexus, which is subsequently reorganized into mature stable network. Although it known that integrin-mediated cell–matrix interactions are indispensable for embryonic angiogenesis, little about function integrins in different steps vascular morphogenesis. Here, by investigating...
Abstract Blood vessels are essential for blood circulation but also control organ growth, homeostasis, and regeneration, which has been attributed to the release of paracrine signals by endothelial cells. Endothelial tubules associated with specialised mesenchymal cells, termed pericytes, help maintain vessel wall integrity. Here we identify pericytes as regulators epithelial morphogenesis in postnatal lung. Mice lacking expression Hippo pathway components YAP TAZ show defective...
Asbestos-associated diseases remain a social burden worldwide. Our previous studies identified asbestos-induced iron-rich milieu for mesothelial cells with ceaseless macrophage ferroptosis. However, molecular mechanisms how this mutagenic influences have not been elucidated yet. Here, we propose novel mechanism that extracellular vesicles (EVs) mediate asbestos-associated factors to cells. In mice model of intraperitoneal crocidolite injection, highly expressed CD63, an exosomal marker. We...
Blood vessels are integrated into different organ environments with distinct properties and physiology (Augustin Koh, 2017). A striking example of organ-specific specialization is the bone vasculature where certain molecular signals yield opposite effect as in other tissues (Glomski et al., 2011; Kusumbe 2014; Ramasamy 2014). Here, we show that transcriptional coregulators Yap1 Taz, components Hippo pathway, suppress vascular growth hypoxic microenvironment bone, contrast to their...
To maintain and restore skeletal muscle mass function is essential for healthy aging. We have found that myonectin acts as a cardioprotective myokine. Here, we investigate the effect of on atrophy in various male mouse models dysfunction. Disruption exacerbates age-associated, sciatic denervation-induced or dexamethasone (DEX)-induced models. Myonectin deficiency also contributes to exacerbated mitochondrial dysfunction reduces expression biogenesis-associated genes including PGC1α...
Protein kinases play pivotal roles in numerous cellular functions; however, the specific substrates of each protein kinase have not been fully elucidated. We developed a novel method called kinase-interacting substrate screening (KISS). Using this method, 356 phosphorylation sites 140 proteins were identified as candidate for Rho-associated (Rho-kinase/ROCK2), including known substrates. The KISS was also applied to additional kinases, PKA, MAPK1, CDK5, CaMK1, PAK7, PKN, LYN, and FYN, lot...
Abstract Sufficient vascular supply is indispensable for brain development and function, whereas dysfunctional blood vessels are associated with human diseases such as malformations, stroke or neurodegeneration. Pericytes capillary-associated mesenchymal cells that limit permeability protect the by preserving blood-brain barrier integrity. Loss of pericytes has been linked to neurodegenerative changes in genetically modified mice. Here, we report postnatal inactivation Rbpj gene, encoding...
Myofibroblasts have roles in tissue repair following damage associated with ischemia, aging, and inflammation also promote fibrosis stiffening, causing organ dysfunction. One source of myofibroblasts is mesenchymal stromal/stem cells that exist as resident fibroblasts multiple tissues. We previously identified meflin (mesenchymal stromal cell- fibroblast-expressing Linx paralogue), a glycosylphosphatidylinositol-anchored membrane protein, specific marker regulator their undifferentiated...
Declining bone mass is associated with aging and osteoporosis, a disease characterized by progressive weakening of the skeleton increased fracture incidence. Growth lifelong homeostasis rely on interactions between different cell types including vascular cells mesenchymal stromal (MSCs). As these involve Notch signaling, we have explored whether treatment secreted ligand proteins can enhance osteogenesis in adult mice. We show that bone-targeting, high affinity version Delta-like 4, termed...
Numb has been implicated in cortical neurogenesis during nervous system development, as a result of its asymmetric partitioning and antagonizing Notch signaling. Recent studies have revealed that functions clathrin-dependent endocytosis by binding to the AP-2 complex. is also expressed postmitotic neurons plays role axonal growth. However, later stages neuronal development remain unknown. Here, we report specifically localizes dendritic spines cultured hippocampal spine morphogenesis,...
The small GTP-binding protein Rho plays a crucial role in wide variety of cellular functions through various effector proteins. Rho-kinase is key Rho, which composed two isoforms, ROCK1 and ROCK2. To clarify the site action ROCK2, we performed immunofluorescence immunoelectron microscopic analyses using isoform-specific antibodies mouse tissues. In large intestines, immunoreactivity was predominantly identified epithelial cells, ROCK2 negligible. these distributed on plasma membranes, while...
Rationale: It is well established that the migration and proliferation of vascular smooth muscle cells (VSMCs) have major roles in remodeling process. Our previous study showed Akt substrate Girdin, which expressed VSMCs endothelial cells, essential for postnatal angiogenesis. However, function Girdin its Akt-mediated phosphorylation their vivo remain to be elucidated. Objective: We investigated using cultured animal models remodeling. Methods Results: The depletion by RNA interference...
The homeostasis of heart and other organs relies on the appropriate provision nutrients functional specialization local vasculature. Here, we have used mouse genetics, imaging cell biology approaches to investigate how in adult is controlled by endothelial EphB4 its ligand ephrin-B2, which are known regulators vascular morphogenesis arteriovenous differentiation during development. We show that inducible cell-specific inactivation Ephb4 mice compatible with survival, but leads rupturing...
Abstract Background The proliferation of cancer-associated fibroblasts (CAFs) hampers drug delivery and anti-tumor immunity, inducing tumor resistance to immune checkpoint blockade (ICB) therapy. However, it has remained a challenge develop therapeutics that specifically target or modulate CAFs. Methods We investigated the involvement Meflin + cancer-restraining CAFs (rCAFs) in ICB efficacy patients with clear cell renal carcinoma (ccRCC) urothelial (UC). examined effects Am80 (a synthetic...
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...
Cell migration is essential for various physiological and pathological processes. Polarization in motile cells requires the coordination of several key signaling molecules, including RhoA small GTPases phosphoinositides. Although participates a front–rear polarization migrating cells, little known about functional interaction between lipid turnover. We find here that src-homology 2–containing inositol-5-phosphatase 2 (SHIP2) interacts with GTP-dependent manner. The association SHIP2 observed...
Cell migration is a critical cellular process that determines embryonic development and the progression of human diseases. Therefore, cell- or context-specific mechanisms by which multiple promigratory proteins differentially regulate cell must be analyzed in detail. Girdin (girders actin filaments) (also termed GIV, Gα-interacting vesicle associated protein) an actin-binding protein regulates various cells such as endothelial cells, smooth muscle neuroblasts, cancer cells. Here we show...
RhoA is transiently activated by specific extracellular signals such as endothelin-1 (ET-1) in vascular smooth muscle cells. RhoGAP negatively regulates activity: thus, becomes the GDP-bound inactive form afterward. Sustained activation of induced with high doses and implicated certain diseases vasospasms. However, it remains largely unknown how prolonged induced. Here we show that Rho-kinase, an effector RhoA, phosphorylated p190A at Ser1150 attenuated activity COS7 Binding Rnd to thought...
Protein kinases are major components of signal transduction pathways in multiple cellular processes. Kinases directly interact with and phosphorylate downstream substrates, thus modulating their functions. Despite the importance identifying substrates order to more fully understand signaling network respective kinases, efficient methods search for remain poorly explored.We combined mass spectrometry affinity column chromatography catalytic domain protein screen potential substrates. Using...
Axon formation is one of the most important events in neuronal polarization and regulated by signaling molecules involved cytoskeletal rearrangement protein transport. We previously found that Partition-defective 3 (Par3) associated with KIF3A (kinesin-2) transported into nascent axon a KIF3A-dependent fashion. Par3 interacts Rac-specific guanine nucleotide-exchange factors (GEFs) Tiam1/2, which activate Rac1, participates cultured hippocampal neurons. However, regulatory mechanism...
Chronic fibrotic tissue disrupts various organ functions. Despite significant advances in therapies, mortality and morbidity due to heart failure remain high, resulting poor quality of life. Beyond the cardiomyocyte-centric view failure, it is now accepted that alterations interstitial extracellular matrix (ECM) also play a major role development failure. Here, we show protein kinase N (PKN) expressed cardiac fibroblasts. Furthermore, PKN mediates conversion fibroblasts into myofibroblasts,...
Abstract Chronic kidney disease is a life‐threatening worldwide. PPARα crucial transcriptional regulator of lipid metabolism and inflammation. Here, we examine whether novel selective modulator, pemafibrate modulates renal injury in model unilateral ureteral obstruction (UUO). Administration to wild‐type (WT) mice led reduction dysfunction fibrosis after UUO with accompanying increases plasma levels fibroblast growth factor (FGF) 21 ketone body β‐hydroxybutyrate (BHB). Treatment WT FGF21 or...