A5004709523- Hormonal Regulation and Hypertension
- Ion Transport and Channel Regulation
- Electrolyte and hormonal disorders
- Sodium Intake and Health
- Epigenetics and DNA Methylation
- Chronic Kidney Disease and Diabetes
- Renin-Angiotensin System Studies
- Birth, Development, and Health
- ATP Synthase and ATPases Research
- Eosinophilic Disorders and Syndromes
- Dialysis and Renal Disease Management
- Systemic Sclerosis and Related Diseases
- IgG4-Related and Inflammatory Diseases
- Parathyroid Disorders and Treatments
- Celiac Disease Research and Management
- T-cell and Retrovirus Studies
- Pregnancy and preeclampsia studies
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Gestational Diabetes Research and Management
- Pancreatic function and diabetes
- Vasculitis and related conditions
- Biomedical and Chemical Research
- Genetic Syndromes and Imprinting
- Inflammatory Myopathies and Dermatomyositis
- Renal and related cancers
The University of Tokyo
2013-2024
Kyorin University
2024
Japan Agency for Medical Research and Development
2017
International University of Health and Welfare
2017
University of Zurich
2017
National Defense Medical College
2017
Vanderbilt University
2017
Utano Hospital
2017
Juntendo University
2015
Japan Science and Technology Agency
2015
Hypertension is a leading contributor to cardiovascular mortality worldwide. Despite this, its underlying mechanism(s) and the role of excess salt in cardiorenal dysfunction are unclear. Previously, we have identified cross-talk between mineralocorticoid receptor (MR), nuclear transcription factor regulated by steroid aldosterone, small GTPase Rac1, which implicated proteinuric kidney disease. We here show that high-salt loading activates Rac1 kidneys rodent models salt-sensitive...
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...
Experiments with hyperaldosteronemic animals suggest that, despite lowering plasma aldosterone, salt worsens renal injury by paradoxical activation of the mineralocorticoid receptor (MR). Salt and aldosterone synergistically contribute to impairment through Rac1-mediated MR, but whether angiotensin II also promotes this mechanism is unknown. Here, we placed II-overproducing double transgenic Tsukuba hypertensive mice on a low- or high-salt intake for 6 weeks treated some adrenalectomy, MR...
Overactivation of the mineralocorticoid receptor signaling is implicated in cardiovascular disease, including hypertensive heart disease. Oxidative stress suggested to augment signal transduction, but precise mechanisms remain unclear. Mineralocorticoid activity regulated by multiple factors, addition plasma ligand levels. We previously identified Rac1 GTPase as a modulator activity. Here we show that oxidative induces activation ligand-independent, Rac1-depenent manner cardiomyocytes....
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...
[Figure: see text].
♦Background Morphology changes of the peritoneal membrane after long-term dialysis (PD) consist denudation mesothelial cells, interstitial sclerosis, and hyalinizing vasculopathy. Those are considered to be result uremia bioincompatible effects conventional acidic lactate-buffered dialysate with glucose degradation products (GDPs). In last decade, biocompatible neutral pH low GDPs has become widely used. Clinical practice been modified in Japan, especially for anuric patients, now includes...
<b><i>Background/Aims:</i></b> Obesity and diabetes are intimately interrelated, independent risk factors for kidney disease. Overactivation of mineralocorticoid receptor (MR) is implicated in end organ damage both pathologies. But the underlying mechanism MR activation remains uncertain. We explored involvement Rac1, which we previously identified as a ligand-independent activator, renal vitro vivo. <b><i>Methods:</i></b> evaluated activity...
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...
A 68-year-old Japanese woman with asthma of recent onset and a long history membranous glomerulonephropathy (MN) was admitted because multifocal pulmonary infiltrates, marked eosinophilia, mild renal dysfunction, rash on her feet, right median nerve paralysis. Although MPO- PR3-ANCA were negative, skin biopsy demonstrated leukocytoclastic vasculitis Churg-Strauss Syndrome (CSS) diagnosed. She also had salivary gland swelling high serum IgG4 level. Renal revealed MN eosinophil-rich...
Genome-wide analysis of renal sodium-transporting system has identified specific variations Mendelian hypertensive disorders, including HSD11B2 gene variants in apparent mineralocorticoid excess. However, these genetic extrarenal tissue can be involved developing hypertension, as demonstrated former studies using global and brain-specific Hsd11b2 knockout rodents. To re-examine the importance dysfunction on we generated kidney-specific mice. The mice exhibited systemic which was abolished by...
The renin-angiotensin-aldosterone system has an important role in the control of fluid homeostasis and BP during volume depletion. Dietary salt restriction elevates circulating angiotensin II (AngII) aldosterone levels, increasing levels Cl − /HCO 3 exchanger pendrin β -intercalated cells Na + -Cl cotransporter (NCC) distal convoluted tubules. However, independent roles AngII regulating these remain unclear. In C57BL/6J mice receiving a low-salt diet or infusion, we evaluated membrane...
Significance Statement Pendrin expressed in renal β -intercalated cells is involved sodium chloride reabsorption distal nephron, and plays an essential role fluid homeostasis BP control conjunction with cotransporter convoluted tubules. Using intercalated cell–specific mineralocorticoid receptor knockout mice, the authors found two distinct pathways of pendrin activation: by angiotensin II elevation, mediated cells, hypokalemic alkalosis, principal cells. Moreover, they demonstrated that...
Introduction Renal tubular injury contributes to the decline in kidney function patients with diabetes. Cell type-specific DNA methylation patterns have been used calculate proportions of particular cell types. In this study, we developed a method detect renal diabetes by detecting exfoliated cells shed into urine based on cell-specific patterns. Research design and methods We identified specific for human proximal through compartment-specific methylome analysis. next determined levels...
Epigenetic modulation may underlie the progression of diabetic nephropathy (DN). Involvement TGFB1 in mesangial fibrosis DN led us to hypothesize that Tgfb1 DNA demethylation contributes DN. In primary cells from (db/db) mouse kidneys, and upregulation mRNA progressed simultaneously. USF1 binding site promoter region were demethylated, increased, with decreased DNMT1 db/db compared control. Given downregulation expression by folic acid, antioxidant Tempol reversed demethylation, increased...
We report a case in whom slow correction of hyponatremia (5 mmol/day for 3 days) induced central pontine myelinolysis (CPM). After the diagnosis was confirmed by imaging, we started to relower serum Na that completely recovered sign and symptoms CPM. Rapid sodium is known be associated with However, it may occur even after hyponatremia. Currently, there no standard therapy CPM other than supportive therapy. Other includes sterioid, plasmaphresis IVIG, but these therapies have not been shown...
To investigate the cause of salt sensitivity in a normotensive animal model, we treated rats with low-dose nitric oxide synthase inhibitor, L-NAME, that does not elevate blood pressure per se or induce kidney fibrosis. A high diet increased circulating volume both L-NAME-treated and nontreated animals for first 24 hours. Thereafter, increase persisted only rats. Blood was higher group from start exposure. Within hours loading, L-NAME failed to show vasodilation maintained systemic vascular...
Epigenetic mechanisms are considered to contribute diabetic nephropathy by maintaining memory of poor glycemic control during the early stages diabetes. However, DNA methylation changes in human kidney poorly characterized, because lack cell type-specific analysis. We examined proximal tubules (PTs) purified from patients with and identified differentially methylated CpG sites, given critical role injury. Hypermethylation was observed at sites annotated genes responsible for tubule...
Epigenetic abnormalities have been suggested to mediate metabolic memory observed in diabetic complications. We shown that epigenetic alterations may induce persistent phenotypic changes the proximal tubules of kidneys. In this study, we show pregnane X receptor (PXR), a xenobiotic nuclear receptor, is epigenetically altered and upregulated possible function kidney. PXR has play critical role obesity diabetes; however, its distribution kidney are unknown. normal kidney, Pxr was selectively...
Renal inflammation is known to be involved in salt-induced renal damage, leading end-stage disease. This study aims evaluate the role of anti-inflammatory and renoprotective effects beraprost sodium (BPS), a prostaglandin I2 (PGI2) analog, Dahl salt-sensitive (DS) rats. Five-week-old male DS rats were fed normal-salt diet (0.5% NaCl), high-salt (8% or plus BPS treatment for 3 weeks. could inhibit marked proteinuria injury salt-loaded with elevated blood pressure, accompanied by suppression....