A5030752224- Neurogenesis and neuroplasticity mechanisms
- Adipokines, Inflammation, and Metabolic Diseases
- Adipose Tissue and Metabolism
- Immune cells in cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Nerve injury and regeneration
- Neuroscience and Neuropharmacology Research
- Fibroblast Growth Factor Research
- Retinal Diseases and Treatments
- Angiogenesis and VEGF in Cancer
- Cell Adhesion Molecules Research
- Mesenchymal stem cell research
- Atherosclerosis and Cardiovascular Diseases
- Neurological Disease Mechanisms and Treatments
- Liver Disease Diagnosis and Treatment
- Chronic Kidney Disease and Diabetes
- MicroRNA in disease regulation
- Wound Healing and Treatments
- Neonatal and fetal brain pathology
- Barrier Structure and Function Studies
- Lysosomal Storage Disorders Research
- Immune Cell Function and Interaction
- Regulation of Appetite and Obesity
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Sirtuins and Resveratrol in Medicine
University of Toyama
2015-2024
Community Medical Center
2016
Japan Science and Technology Agency
2004-2010
Tohoku Medical and Pharmaceutical University
2000-2004
Shiga University of Medical Science
1990-2000
Kirin (Japan)
1999
Osaka University
1997
University of Washington
1990-1995
Kyoto University
1993
Lesions of atherosclerosis occur in the innermost layer artery wall and consist primarily proliferated smooth muscle cells surrounded by large amounts connective tissue, numerous lipid-laden macrophages, varying numbers lymphocytes. Growth-regulatory molecules may be involved intimal accumulation proliferation responsible for occlusive lesions atherosclerosis. Platelet-derived growth factor (PDGF) B-chain protein was found within macrophages all stages lesion development both human nonhuman...
Significance We show that vascular pericytes significantly contribute to cancer invasion and metastasis by the mechanism of pericyte–fibroblast transition (PFT). This study proposes this concept indicates pericyte’s role. Vascular were considered remodel tumor vessels toward a mature phenotype. However, once dissociated from their functions within tissue are not known. In present study, we pericytes, detached microvasculatures, underwent differentiation become stromal fibroblasts, which...
Abstract Adipose tissue resident macrophages have important roles in the maintenance of homeostasis and regulate insulin sensitivity for example by secreting pro-inflammatory or anti-inflammatory cytokines. Here, we show that M2-like adipose systemic glucose inhibiting adipocyte progenitor proliferation via CD206/TGFβ signaling pathway. We CD206 + cells are primarily macrophages, ablation improves sensitivity, which was associated with an increased number smaller adipocytes. Mice genetically...
Lipoprotein oxidation is believed to play an important role in atherogenesis. To investigate whether inhibition of low density lipoprotein (LDL) would alter atherogenesis the nonhuman primate, we administered probucol, a potent antioxidant, Macaca nemestrina fed high-fat, high-cholesterol diet. Probucol was half 16 monkeys 14 wk after starting hypercholesterolemic diet, and given daily until they were sacrificed 11 mos. evaluate antioxidant effect resistance isolated plasma LDL vitro...
Recent evidence suggests that treatment with mineralocorticoid receptor antagonist suppressed local inflammation in vascular tissues or cardiomyocytes; therefore, we examined the effect of spironolactone on glucose and lipid metabolism a mouse model diet-induced diabetes nonalcoholic fatty liver disease. C57BL/6 mice were fed either control diet, 60% fat diet 30% fructose water (HFFD), HFFD for 8 wk. demonstrated apparent phenotypes metabolic syndrome, including insulin resistance,...
Abstract Mesenchymal stromal cells (MSCs) in bone marrow are important for homeostasis. Although platelet-derived growth factor (PDGF) has been reported to be involved osteogenic differentiation of MSCs, the role remains controversial and network PDGF signaling MSCs not clarified. To clarify underlying regulatory mechanism MSC functions mediated by PDGF, we deleted receptor (PDGFR)β gene Cre-loxP strategy examined fracture repair. In cultured mRNA expression PDGF-A, -B, -C, -D as well PDGFRα...
Abstract Emerging lines of evidence have shown that extracellular vesicles (EVs) mediate cell-to-cell communication by exporting encapsulated materials, such as microRNAs (miRNAs), to target cells. Endothelial cell-derived EVs (E-EVs) are upregulated in circulating blood different pathological conditions; however, the characteristics and role these E-EVs not yet well understood. In vitro studies were conducted determine inflammation-induced between vascular endothelial cells pericytes/vSMCs....
Skeletal muscle is mainly responsible for insulin-stimulated glucose disposal. Dysfunction in skeletal metabolism especially during obesity contributes to the insulin resistance. Astaxanthin (AX), a natural antioxidant, has been shown ameliorate hepatic resistance obese mice. However, its effects are poorly understood. The current study aimed investigate molecular target of AX ameliorating resistance.We fed 6-week-old male C57BL/6J mice with normal chow (NC) or NC supplemented (NC+AX) and...
Unrelated memories get blurred together If one retrieves two around the same time, a small number of neurons will become involved in both memories. Yokose et al. investigated cellular ensemble mechanisms underlying association between such In mice, population mediates association. Memory traces for independent emotional brain partially overlapped when were retrieved synchronously to create linkage. Suppressing activity overlapping memory trace interrupted linkage without damaging original...
Adipose tissue hypoxia is an important feature of pathological adipose expansion. Hypoxia-inducible factor-1α (HIF-1α) in adipocytes reportedly induces oxidative stress and fibrosis, rather than neoangiogenesis via vascular endothelial growth factor (VEGF)-A. We previously reported that macrophages crown-like structures (CLSs) are both hypoxic inflammatory. In the current study, we examined how macrophage HIF-1α involved high-fat diet (HFD)–induced inflammation, neovascularization, hypoxia,...
Although platelet-derived growth factor receptor beta (PDGFR-β) mediates the recruitment of vascular pericytes into ischemic lesion to restore blood-brain barrier (BBB) dysfunction, its mechanisms still remain elusive. Compared with control PDGFR-βfloxed/floxed mice (Floxed), postnatally induced systemic PDGFR-β knockout (Esr-KO) not only showed severe brain edema, neurologic functional deficits, decreased expression tight junction (TJ) proteins, abundant endothelial transcytosis, and...
Although platelet-derived growth factors (PDGFs) and receptors (PDGFRs) are abundantly expressed in the central nervous system, their functions largely remain elusive. We investigated role of PDGFR-β tissue responses functional recovery after photothrombolic middle cerebral artery occlusion (MCAO). In normal adult mouse brain, was mainly localized neurons pericyte/vascular smooth muscle cells (PC/vSMCs). From 3 to 28 days MCAO, postnatally induced systemic knockout mice (Esr-KO) exhibited...
Age-related loss of ovarian function promotes adiposity and insulin resistance in women. Estrogen (E(2)) directly enhances sensitivity suppresses lipogenesis peripheral tissues. Recently, the central actions E(2) regulation energy homeostasis are becoming clearer; however, functional relevance degree contribution vs. currently unknown. Therefore, we prepared analyzed four groups mice. 1) CONTROL: sham-operated mice fed a regular diet, 2) OVX-HF: ovariectomized (OVX) 60% high-fat diet (HF),...
Abstract The neuroprotective effects of platelet‐derived growth factor (PDGF) and the major signaling pathways involved in these were examined using primary cultured mouse cortical neurons subjected to H 2 O ‐induced oxidative stress. specific function PDGF β‐receptor (PDGFR‐β) was by selective deletion corresponding gene Cre‐loxP system vitro. In wild‐type neurons, PDGF‐BB enhanced survival suppressed caspase‐3 activation. prosurvival effect PDGF‐AA less than that PDGF‐BB. highly activated...
ABSTRACT Background and objective: In asthma, reduced histone deacetylase activity enhanced acetyltransferase in the lungs have been reported. However, precise function of Sirtuin 1 (Sirt1), a class III deacetylase, effect Sirt1 activator SRT1720 on allergic inflammation not fully elucidated. Methods: The SRT1720, synthetic Sirt1, an ovalbumin (OVA)‐induced asthma mouse model was investigated. resveratrol OVA stimulation splenocytes from OVA‐sensitized challenged mice also examined. Results:...
Platelet-derived growth factor (PDGF) is a key in angiogenesis; however, its role adult obesity remains unclear. In order to clarify pathophysiological role, we investigated the significance of PDGF receptor β (PDGFRβ) adipose tissue expansion and glucose metabolism. Mature vessels epididymal white (eWAT) were tightly wrapped with pericytes normal mice. Pericyte desorption from subsequent proliferation endothelial cells markedly increased eWAT diet-induced obese Analyses flow cytometry...
Abstract Pericytes are believed to originate from either mesenchymal or neural crest cells. It has recently been reported that pericytes play important roles in the central nervous system (CNS) by regulating blood-brain barrier homeostasis and blood flow at capillary level. However, origin of CNS microvascular mechanism their recruitment remain unknown. Here, we show a new source cerebrovascular during neurogenesis. In embryonic day 10.5 mouse embryos, CD31 + F4/80 hematopoietic lineage...
Abstract Isoliquiritigenin (ILG) is a flavonoid derived from Glycyrrhiza uralensis and potently suppresses NLRP3 inflammasome activation resulting in the improvement of diet-induced adipose tissue inflammation. However, whether ILG affects other pathways besides inflammation unknown. We here show that by affecting paracrine loop containing saturated fatty acids TNF-α using co-culture composed adipocytes macrophages. suppressed inflammatory changes induced through inhibition NF-κB activation....
Abstract Platelet derived growth factor (PDGF) plays a pivotal role in the remodeling of connective tissues. Emerging data indicate distinctive PDGF receptor-α (PDGFRα) this process. In present study, Pdgfra gene was systemically inactivated adult mouse (α-KO mouse) and PDGFRα examined subcutaneously implanted sponge matrices. expressed fibroblasts -preserving control mice (Flox mice), significantly reduced sponges α-KO mice. Neovascularized areas were largely suppressed than Flox mice,...
Chronic activation of the IL‐1β system in adipose tissue on metabolic disorders is well demonstrated. However, a mechanism for its expression and has remained unexplored. Here, we demonstrate that transcript was enriched neutrophils white (WAT) from lean mice. Mechanistically, interaction with adipocytes induced via NF‐κB pathway. Lipolysis accumulated prior to macrophages WAT produced high levels an inflammasome Leukotriene B 4 (LTB ) production also contributed neutrophil accumulation....
Abstract Obesity and insulin resistance are associated with dysbiosis of the gut microbiota impaired intestinal barrier function. Herein, we report that Bofutsushosan (BFT), a Japanese herbal medicine, Kampo, which has been clinically used for constipation in Asian countries, ameliorates glucose metabolism mice diet–induced obesity. A 16S rRNA sequence analysis fecal samples showed BFT dramatically increased relative abundance Verrucomicrobia, was mainly bloom Akkermansia muciniphila (AKK)....
Oligodendrocyte progenitor cells (OPCs) are widely distributed of ramified morphology in adult brain that express PDGFRα and NG2. They retain mitotic activities adulthood contribute to oligodendrogenesis myelin turnover; however, the regulatory mechanisms their cell dynamics largely remain unknown. Here, we found global Pdgfra inactivation mice rapidly led elimination OPCs due synchronous maturation toward oligodendrocytes. Surprisingly, OPC densities were robustly reconstituted by active...
Abstract Muscle regeneration requires the coordination of muscle stem cells, mesenchymal fibro-adipogenic progenitors (FAPs), and macrophages. How macrophages regulate paracrine secretion FAPs during recovery process remains elusive. Herein, we systemically investigated communication between CD206 + M2-like using a transgenic mouse model. Depletion or deletion macrophages-specific TGF-β1 gene induces myogenesis regeneration. We show that depletion activates activated secrete follistatin,...