A5014151765- Hormonal Regulation and Hypertension
- Circadian rhythm and melatonin
- Renin-Angiotensin System Studies
- Adrenal and Paraganglionic Tumors
- Blood Pressure and Hypertension Studies
- Dietary Effects on Health
- Genetics, Aging, and Longevity in Model Organisms
- Adrenal Hormones and Disorders
- ATP Synthase and ATPases Research
- Receptor Mechanisms and Signaling
- Cardiovascular Health and Disease Prevention
- Adipose Tissue and Metabolism
- Diet and metabolism studies
- Birth, Development, and Health
- Diet, Metabolism, and Disease
- Liver Disease Diagnosis and Treatment
- Renal Diseases and Glomerulopathies
- Epigenetics and DNA Methylation
- Diabetes Treatment and Management
- Ion Transport and Channel Regulation
- Neuroendocrine regulation and behavior
- Pituitary Gland Disorders and Treatments
- Spaceflight effects on biology
- Sodium Intake and Health
- Renal and Vascular Pathologies
Keio University
2012-2025
University of California, Irvine
2014-2023
Keio University Hospital
2023
Inserm
2020
Biogem
2019
Japan Science and Technology Agency
2010
Osaka University
2010
Doshisha Women's College of Liberal Arts
2010
Food Research Institute
2010
Rationale : The (pro)renin receptor [(P)RR], encoded in ATP6AP2 , plays a key role the activation of local renin-angiotensin system (RAS). A truncated form (P)RR, termed M8.9, was also found to be associated with vacuolar H + -ATPase (V-ATPase), implicating non–RAS-related function ATP6AP2. Objective We investigated (P)RR/ATP6AP2 murine cardiomyocytes. Methods and Results Cardiomyocyte-specific ablation Atp6ap2 resulted lethal heart failure; cardiomyocytes contained RAB7-...
The prorenin receptor is an accessory subunit of the vacuolar H+-ATPase, suggesting that it has fundamental functions beyond activation local renin-angiotensin system. Podocytes express receptor, but its function in these cells unknown. Here, podocyte-specific, conditional, receptor-knockout mice died kidney failure and severe proteinuria within 4 weeks birth. podocytes exhibited foot process effacement with reduced altered localization slit-diaphragm proteins nephrin podocin. Furthermore,...
The circadian clock operates as intrinsic time-keeping machinery to preserve homeostasis in response the changing environment. While food is a known zeitgeber for clocks peripheral tissues, it remains unclear how lack of influences function. We demonstrate that transcriptional fasting through molecular mechanisms are distinct from time-restricted feeding regimens. First, affects core genes and proteins, resulting blunted rhythmicity BMAL1 REV-ERBα both liver skeletal muscle. Second, induces...
The S-adenosylhomocysteine (SAH) hydrolyzing enzyme AHCY functionally links the circadian clock to methionine metabolism.
Binge drinking and chronic exposure to ethanol contribute alcoholic liver diseases (ALDs). A potential link between ALDs circadian disruption has been observed, though how different patterns of alcohol consumption differentially impact hepatic metabolism remains virtually unexplored. Using acute versus feeding, we reveal differential reprogramming the transcriptome in liver. Specifically, rewiring diurnal SREBP transcriptional pathway leads distinct signatures acetyl-CoA that are translated...
Significance Nutrition and the body clock are deeply intertwined, both impinging on our physiological health. Food composition can dramatically rewire peripheral metabolism; however, whether food challenges impact circadian metabolism of master in suprachiasmatic nucleus (SCN) or other brain areas has not been fully explored. Here we analyzed complete diurnal metabolome SCN medial prefrontal cortex (mPFC) mice fed a balanced diet high-fat (HFD). Strikingly, data reveal unexpected daily...
A direct renin inhibitor (DRI) had a benefit in decreasing albuminuria type 2 diabetic patients having already been treated with angiotensin (Ang) II 1 receptor blocker (ARB), suggesting that aliskiren may have another effect other than blockade of the traditional renin–angiotensin system (RAS). Recently, prorenin bound to (pro)renin ((P)RR) was found and shown evoke two pathways; generation Ang peptides receptor-dependent activation extracellular signal–related protein kinase (ERK). Because...
The ATPase 6 accessory protein 2 (ATP6AP2)/(pro)renin receptor (PRR) is essential for the biogenesis of active vacuolar H+-ATPase (V-ATPase). Genetic deletion ATP6AP2/PRR causes V-ATPase dysfunction and compromises vesicular acidification. Here, we characterized domains involved in biogenesis. Three forms were found intracellularly: full-length N- C-terminal fragments furin cleavage products, with N-terminal fragment secreted extracellularly. did not affect stability subunits. extracellular...
<i>Background/Aims:</i> This study was conducted to determine the effect of telmisartan on cardio-ankle vascular index (CAVI), a novel blood pressure (BP)-independent marker for arterial stiffness in hypertensive patients. <i>Methods:</i> One hundred consecutive patients were randomly assigned either group treated with calcium channel blocker (CCB)-based therapy or telmisartan-based therapy. Clinical and biological parameters then measured before 12 months after start...
Abstract To extend life expectancy and ensure healthy aging, it is crucial to prevent minimize age‐induced skeletal muscle atrophy, also known as sarcopenia. However, the disease's molecular mechanism remains unclear. The age‐related Wnt/β‐catenin signaling pathway has been recently shown be activated by (pro)renin receptor ((P)RR). We report here that (P)RR expression was increased in atrophied muscles of aged mice humans. Therefore, we developed a gain‐of‐function model sarcopenia via...
Distinct metabolic conditions rewire circadian-clock-controlled signaling pathways leading to the de novo construction of signal transduction networks. However, it remains unclear whether hallmarks unique pluripotent stem cells (PSCs) are connected clock functions. Reprogramming somatic a state, here we highlighted non-canonical functions circadian repressor CRY1 specific PSCs. Metabolic reprogramming, including AMPK inactivation and SREBP1 activation, was coupled with accumulation in...
Drinking hydrogen (H2)-rich water is a common way to consume H2. Although many studies have shown efficacy of drinking H2-rich in neuropsychiatric and endocrine metabolic disorders, their authenticity has been questioned because none examined the associated pharmacokinetics Therefore, we performed first study investigate H2 pigs given an glucose solution with aim extrapolate findings humans. We inserted blood collection catheters into jejunal portal veins, suprahepatic inferior vena cava,...