A5013334721- Hormonal Regulation and Hypertension
- Nitric Oxide and Endothelin Effects
- Ion Transport and Channel Regulation
- Epigenetics and DNA Methylation
- Electrolyte and hormonal disorders
- Chronic Kidney Disease and Diabetes
- Renal and related cancers
- Sodium Intake and Health
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cardiac Ischemia and Reperfusion
- Parathyroid Disorders and Treatments
- Histone Deacetylase Inhibitors Research
- Renin-Angiotensin System Studies
- Angiogenesis and VEGF in Cancer
- Eicosanoids and Hypertension Pharmacology
- Genetic and Kidney Cyst Diseases
- Pluripotent Stem Cells Research
- Mesenchymal stem cell research
- Biomedical Research and Pathophysiology
- Birth, Development, and Health
- Genomics, phytochemicals, and oxidative stress
- Neurogenesis and neuroplasticity mechanisms
- Cell Adhesion Molecules Research
- Nuclear Receptors and Signaling
- RNA Interference and Gene Delivery
International University of Health and Welfare
2017-2024
The University of Tokyo
2009-2022
University of Zurich
2017
Vanderbilt University
2017
Japan Agency for Medical Research and Development
2017
National Defense Medical College
2017
Japan Science and Technology Agency
2015
Shinshu University
2015
Juntendo University
2015
Nagase (Japan)
2015
Human umbilical vein endothelial cells (HUVEC) express functional receptors to leptin, the product of ob gene. As human obesity is associated with atherosclerosis and hyperleptinemia, we investigated whether in addition its angiogenic properties, exerts atherogenic effects through generation oxidative stress cells. In HUVEC leptin increased accumulation reactive oxygen species (ROS), as assessed by oxidation 2', 7'- dichlorodihydrofluorescein, a time- concentration-dependent manner....
We have examined the effects of sex hormones on calcium‐dependent NO production and protein levels synthase in cultured human aortic endothelial cells, which were treated with various doses 17 β ‐estradiol testosterone for 8–48 h. Treatment enhanced production, but had exerted no effect. Western blot using monoclonal anti‐human antibody clarified that increased by treatment was accompanied protein. Our results provide evidence can be regulated estrogens.
Background Platelet-derived growth factor (PDGF) and superoxide anion (O 2 ·− ) have been implicated in vascular diseases. We investigated whether PDGF stimulates the production of O human aortic smooth muscle cells (HSMCs) leads this way to activation nuclear factor–κB (NF-κB) induction monocyte chemoattractant protein 1 (MCP-1) PDGF-stimulated HSMCs. Methods Results PDGF-AB concentration- time-dependently stimulated generation from The stimulatory effect was mimicked by PDGF-BB but not...
Vascular endothelial growth factor (VEGF) has been suggested to play a role in the pathogenesis of diabetic vascular complications. In present study, we investigated whether expression monocyte chemoattractant protein-1 (MCP-1), chemokine that proposed recruit leukocytes sites inflammation, neovascularization, and injury, can be modulated by VEGF bovine retinal microvascular cells (BRECs). induced MCP-1 mRNA BRECs concentration- time-dependent manner. Secretion into culture medium treated...
Histone acetylation plays an important role in regulating gene expressions by modulating chromatin structure. deacetylase (HDAC) inhibitors have been reported to antifibrogenic effect some organs, such as the liver, skin, and lung, but underlying mechanisms remain be clarified. In kidney, bone morphologic protein 7 (BMP-7) hepatocyte growth factor are antagonize TGF-beta1-induced tubular epithelial-to-mesenchymal transition (EMT), nothing is known concerning of HDAC on EMT. It was shown that...
Enhanced matrix metalloproteinases (MMPs) can cause vasogenic edema and hemorrhagic transformation after cerebral ischemia, affect the extent of ischemic injury. We hypothesized that endogenous MMP inhibitors, tissue inhibitor MMPs (TIMPs), were essential to protect against blood-brain barrier (BBB) disruption ischemia by regulating activities MMPs. confirmed transition MMP-2 MMP-9, TIMPs family 30 mins middle artery occlusion, elucidated function TIMP-1 TIMP-2 in focal using TIMP-1(-/-)...
Histone deacetylase (HDAC) regulates gene expression by modifying chromatin structure. Although changes in the and activities of HDAC may affect course kidney disease, role tubulointerstitial injury has not been explored. We therefore investigated alterations determined effects inhibition on induced unilateral ureteral obstruction. The induction HDAC1 HDAC2, accompanied a decrease histone acetylation was observed kidneys injured Immunohistochemical analysis revealed that HDAC2 were renal...
Epigenetic mechanisms may underlie the progression of diabetic kidney disease. Because is a heterogeneous organ with different cell types, we investigated DNA methylation status in type-specific manner. We first identified genes specifically demethylated normal proximal tubules obtained from control db/m mice, and next delineated candidate disease-modifying bearing aberrant induced by diabetes using db/db mice. Genes involved glucose metabolism, including Sglt2, Pck1, G6pc, were selectively...
High blood pressure is one of the major risk factors for atherosclerosis. In this study, we examined effects on cell proliferation and DNA synthesis in cultured rat vascular smooth muscle cells. Pressure without shear stress stretch promotes a pressure-dependent manner. Pressure-induced was inhibited significantly by phospholipase C (PLC) inhibitor 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate, protein kinase H-7, 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine, staurosporine, tyrosine...
Musculin/MyoR is a new member of basic helix-loop-helix transcription factors, and its expression limited to skeletal muscle precursors. Here, we report that musculin/MyoR expressed in adult kidney side population (SP) cells can regulate their function. SP phenotype be used purify stem cell–rich fractions. Microarray analysis clarified was exclusively cells, the resided renal interstitial space. Musculin/MyoR-positive were decreased acute failure, but infusion increased...
There is increasing evidence for a crucial role of aberrant mineralocorticoid receptor (MR) activation in heart failure, with clinical studies showing beneficial effects MR blockade. However, the mechanisms failure remain unclear. In this study, we observed that small GTPase Rac1 contributes to myocardial activation, whereas Rac1-MR pathway leads cardiac dysfunction. Mouse hearts subjected chronic pressure overload induced by transverse aortic constriction showed and increased nuclear...
Aging is associated with a high prevalence of hypertension due to elevated susceptibility BP dietary salt, but its mechanism unknown. Serum levels Klotho, an anti-aging factor, decline age. We found that salt (HS) increased in aged mice and young heterozygous Klotho-knockout was vascular expression Wnt5a p-MYPT1, which indicate RhoA activity. Not only the Wnt inhibitor LGK974 antagonist Box5 Klotho supplementation inhibits HS-induced elevation, similarly Rho kinase fasudil, reduced p-MYPT1...
Abstract The effect of pure pressure without shear stress or stretch on the release endothelin-1 was investigated. Elevation significantly enhanced from cultured human umbilical vein endothelial cells. A calcium channel blocker, nifedipine, and a putative stretch-activated gadolinium, did not affect pressure-induced increase. On other hand, phospholipase C inhibitor, 2-nitro-4-carboxyphenyl- N , -diphenylcarbamate, protein kinase inhibitors, 1-5-(isoquinolinylsulfonyl)-2-methylpiperazine...
Loss of glomerular endothelial cells has been suggested to contribute the progression injury. Although therapeutic angiogenesis induced by administration bone marrow-derived progenitor observed in disease models injury, effects on renal have not clarified. Whether culture-modified marrow mononuclear would mitigate injury anti-Thy1.1 nephritis was investigated. After cultivation under conditions that promote cell growth, were labeled with CM-DiI, a fluorescence marker, and injected into left...
Kidneys damaged by ischemia have the potential to regenerate through a mechanism involving intrarenal induction of protective factors, including bone morphogenetic protein-7 (BMP7). Epigenetic changes, such as alterations in histone modifications, also been shown play role various pathologic conditions, but their involvement ischemic injury and regeneration remains unknown. This study investigated whether changes acetylation, regulated acetyltransferase deacetylase (HDAC), are induced renal...
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Abstract The effect of cyclosporin A on induction nitric oxide synthase in rat aortic smooth muscle cells was examined. combination interleukin-1α (100 U/mL) and tumor necrosis factor−α (5000 induced accumulation nitrite/nitrate, the stable end products oxide, culture media within 48 hours. Cyclosporin inhibited this nitrite/nitrate a concentration-dependent manner with an IC 50 4×10 −7 mol/L when applied simultaneously cytokines. expression inducible messenger RNA (mRNA) by factor–α...
Abstract —Recent reports suggest that the increased production of reactive oxygen species (ROS) in vascular wall may contribute to functional and structural changes associated with hypertension atherosclerosis. Although glucocorticoid therapy can promote atherosclerosis, protective effects these compounds on lesion formation have been reported. In present study, we investigated whether ROS cultured human aortic smooth muscle cells (HSMCs) be modulated by glucocorticoids. Pretreatment HSMCs...
Maternal malnutrition, which causes prenatal exposure to excessive glucocorticoid, induces adverse metabolic programming, leading hypertension in offspring. In offspring of pregnant rats receiving a low-protein diet or dexamethasone, synthetic mRNA expression angiotensin receptor type 1a (Agtr1a) the paraventricular nucleus (PVN) hypothalamus was upregulated, concurrent with reduced DNA methyltransferase 3a (Dnmt3a), binding DNMT3a Agtr1a gene, and demethylation. Salt loading increased BP...
Bone morphogenic protein (BMP)-7 is expressed in the adult kidney and reverses chronic renal injury when given exogenously. Here, we report that a histone deacetylase inhibitor, trichostatin A (TSA), attenuates injury, part, by augmenting expression of BMP-7 side population (SP) cells. We induced accelerated nephrotoxic serum nephritis (NTN) C57BL/6 mice treated them with TSA for 3 weeks. Compared vehicle-treated NTN mice, treatment prevented progression proteinuria, glomerulosclerosis,...
Treatment with DAPT, an inhibitor of the Notch-activating enzyme, γ-secretase is known to reduce damage ischemic brain. However, molecular mechanisms supporting this therapeutic effect are not fully understood. Here we demonstrated that Notch/RBP-J signaling activated in NG2+ glial progenitors and reactive astrocytes such as GFAP+ cells, Nestin+ cells RC2+ using reporter mice. 3-day DAPT treatment reduced number but progenitors. BrdU labeling experiments have shown reduction was due...