- Advanced Glycation End Products research
- Neuroendocrine regulation and behavior
- Natural Antidiabetic Agents Studies
- Neuroscience of respiration and sleep
- Chronic Kidney Disease and Diabetes
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Calcium signaling and nucleotide metabolism
- Immune cells in cancer
- Alcohol Consumption and Health Effects
- S100 Proteins and Annexins
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Diabetes and associated disorders
- Neurological Disorders and Treatments
- Fatty Acid Research and Health
- Alzheimer's disease research and treatments
- Immune Response and Inflammation
- Liver Disease Diagnosis and Treatment
- Pancreatic function and diabetes
- Nitric Oxide and Endothelin Effects
- Adenosine and Purinergic Signaling
- Angiogenesis and VEGF in Cancer
- Infant Health and Development
- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
Kanazawa University
2016-2025
Bangladesh Agricultural University
2024
Guangxi University of Chinese Medicine
2024
Tohoku University
1999-2023
Kobe University
2016-2020
Center for Vascular Biology Research
2020
Joslin Diabetes Center
2013-2016
Harvard University
2013-2016
Kanazawa Hospital
2011-2014
Kobe University Hospital
2014
The binding of advanced glycation end-products (AGE) to the receptor for AGE (RAGE) is known deteriorate various cell functions and implicated in pathogenesis diabetic vascular complications. In present study, we show that cellular constituents small vessels, endothelial cells (EC) pericytes express novel splice variants RAGE mRNA coding isoforms lack N-terminal V-type immunoglobulin-like domain (N-truncated) or C-terminal transmembrane (C-truncated), as well full-length mRNA. ratio...
Thrombomodulin (TM) is an endothelial anticoagulant cofactor that promotes thrombin-mediated formation of activated protein C (APC). We have found the N-terminal lectin-like domain (D1) TM has unique antiinflammatory properties. TM, via D1, binds high-mobility group-B1 DNA-binding (HMGB1), a factor closely associated with necrotic cell damage following its release from nucleus, thereby preventing in vitro leukocyte activation, vivo UV irradiation–induced cutaneous inflammation, and...
Vascular complications arising from multiple environmental and genetic factors are responsible for many of the disabilities short life expectancy associated with diabetes mellitus. Here we provide first direct in vivo evidence that interactions between advanced glycation end products (AGEs; nonenzymatically glycosylated protein derivatives formed during prolonged hyperglycemic exposure) their receptor, RAGE, lead to diabetic vascular derangement. We created transgenic mice overexpress human...
The binding of advanced glycation end products (AGE) to the receptor for AGE (RAGE) is known deteriorate various cell functions and implicated in pathogenesis diabetic vascular complications. Here we show that AGE, tumor necrosis factor-α (TNF-α), 17β-estradiol (E2) up-regulated RAGE mRNA protein levels human microvascular endothelial cells ECV304 cells, with stability being essentially invariant. Transient transfection experiments promoter-luciferase chimeras revealed region from nucleotide...
C-C motif chemokine receptor (CCR)2 and its ligand, monocyte chemoattractant protein (MCP)-1, are pivotal for adipose tissue macrophage (ATM) recruitment the development of insulin resistance. However, other systems also may play a role in these processes. In this study, we investigated CCR5 obesity-induced inflammation We analyzed expression levels ligands white (WAT) genetically (ob/ob) high-fat (HF) diet-induced obese (DIO) mice. Furthermore, examined metabolic phenotype Ccr5(-/-) were...
Tumor-associated macrophages (TAMs) of the M2 phenotype are known to promote tumor proliferation and be associated with a poor prognosis in numerous cancers. Here, we investigated whether participate development peritoneal dissemination gastric cancer.The characteristics cancer patients or without were examined by flow cytometry real-time quantitative polymerase chain reaction. The effects on phenotypic changes cell line MKN45 assessed direct indirect co-culture system vitro an vivo mouse...
Abstract Objective: High mobility group box‐1 (HMGB1) plays an important role in triggering inflammatory responses many types of diseases. In this study, we examined the involvement HMGB1 traumatic brain injury (TBI) and evaluated ability intravenously administered neutralizing anti‐HMGB1 monoclonal antibody (mAb) to attenuate injury. Methods: Traumatic was induced rats or mice by fluid percussion. Anti‐HMGB1 mAb control after TBI. Results: remarkably inhibited percussion‐induced edema rats,...
Oxytocin sets the stage for childbirth by initiating uterine contractions, lactation and maternal bonding behaviours. Mice lacking secreted oxcytocin (Oxt-/-, Cd38-/-) or its receptor (Oxtr-/-) fail to nurture. Normal behaviour is restored peripheral replacement in Oxt-/- Cd38-/-, but not Oxtr-/- mice, implying that circulating crosses blood-brain barrier. Exogenous also has behavioural effects humans. However, polypeptides are typically excluded from brain. We show transported into brain...
Advanced glycation endproducts, AGEs, and its specific receptor, RAGE, are involved in diabetic vascular complications. Endogenous secretory esRAGE, has been identified as an alternatively spliced form of shown to act a decoy receptor for AGE. Here, we measured plasma esRAGE level with recently developed enzyme-linked immunosorbent assay (ELISA) examined association atherosclerosis age- gender-matched 203 type 2 134 nondiabetic subjects.Plasma was inversely associated carotid or femoral...
This study was undertaken to determine whether and how advanced glycation end products (AGE), senescent macroproteins accumulated in various tissues under hyperglycemic states, cause angiogenesis, the principal vascular derangement diabetic microangiopathy. We first prepared AGE-bovine serum albumin (BSA) anti-AGE antiserum using AGE-RNase A. Then AGE-BSA administered human skin microvascular endothelial cells culture, their growth examined. The AGE-BSA, but not nonglycated BSA, found induce...
Diabetic nephropathy is a major microvascular complication in long-standing diabetic patients who eventually undergo renal dialysis or transplantation. To prevent development of this disease and to improve advanced kidney injury, effective therapies directed toward the key molecular target are required. In study, we examined whether inhibition receptor for glycation end products (RAGE) could attenuate changes kidney. Here, show that inactivation RAGE gene mouse model results significant...
OBJECTIVE A multicenter, controlled trial showed that early blockade of the renin-angiotensin system in patients with type 1 diabetes and normoalbuminuria did not retard progression nephropathy, suggesting other mechanism(s) are involved pathogenesis diabetic nephropathy (diabetic nephropathy). We have previously demonstrated endothelial-mesenchymal-transition (EndoMT) contributes to development renal interstitial fibrosis independently microalbuminuria mice streptozotocin (STZ)-induced...
Increases in [Ca2+]i pancreatic beta cells, resulting from Ca2+ mobilization intracellular stores as well influx extracellular sources, are important insulin secretion by glucose. Cyclic ADP-ribose (cADPR), accumulated cells glucose stimulation, has been postulated to serve a second messenger for secretion, and CD38 is thought be involved the cADPR accumulation (Takasawa, S., Tohgo, A., Noguchi, N., Koguma, T., Nata, K., Sugimoto, Yonekura, H., Okamoto, H. (1993) J. Biol. Chem. 268,...
Septic shock is a severe systemic response to bacterial infection. Receptor for advanced glycation end products (RAGE) plays role in immune reactions recognize specific molecular patterns as pathogen recognition receptors. However, the interaction between LPS, bioactive component of cell walls, and RAGE unclear. In this study, we found direct LPS binding by surface plasmon resonance assay, plate competition flow cytometry. increased TNF-α secretion from peritoneal macrophages an NF-κB...
The pathogenesis of pulmonary fibrosis remains unclear. receptor for advanced glycation end-products (RAGE) is a multi-ligand known to be involved in the process fibrotic change several organs, such as peritoneal and kidney fibrosis. aim this study was examine contribution RAGE during acute inflammation chronic phases lung injury induced by intratracheal instillation bleomycin mice. Bleomycin-induced evaluated wild-type RAGE-deficient (RAGE-/-) Bleomycin administration mice caused an initial...
Interaction of RAGE (the receptor for advanced glycation endproducts) with its ligands can promote tumor progression, invasion, and angiogenesis. Although blocking signaling has been proposed as a potential anticancer strategy, functional contributions expression in the microenvironment (TME) have not investigated detail. Here, we evaluated effect genetic depletion TME on growth gliomas. In both invasive noninvasive glioma models, animal survival was prolonged knockout (Ager(-/-)) mice....
Receptor for advanced glycation end products (RAGE) has been shown to be involved in adiposity as well atherosclerosis even nondiabetic conditions. In this study, we examined mechanisms underlying how RAGE regulates and insulin sensitivity. overexpression 3T3-L1 preadipocytes using adenoviral gene transfer accelerated adipocyte hypertrophy, whereas inhibitions of by small interfering RNA significantly decrease hypertrophy. Furthermore, double knockdown high mobility group box-1 S100b, both...