Toshiro Fujita
Shinshu University
Internal medicineEndocrinologySurgeryMolecular biologyRenal functionCardiologyReceptorChemistryMineralocorticoid receptorRenin–angiotensin systemOxidative stressAldosteroneKidney diseaseKidneyAngiotensin IIMedicineBlood pressureBiologyCell biologyPharmacology
872Publications
121H-index
40.6kCitations
Publications 871
Newest
#1Daigoro Hirohama (UTokyo: University of Tokyo)H-Index: 11
#2Mitsuhiro Nishimoto (UTokyo: University of Tokyo)H-Index: 9
Last. Toshiro Fujita (UTokyo: University of Tokyo)H-Index: 121
view all 9 authors...
The progression of diabetic kidney disease (DKD), a leading cause of end-stage kidney disease, involves mineralocorticoid receptor (MR) activation. We previously identified crosstalk between the small guanosine triphosphatase (GTPase) RAS-related C3 botulinus toxin substrate 1 (Rac1) and MR, but the role of Rac1-MR pathway activation in the progression of DKD is not clear. We performed uninephrectomy on type 2 diabetic mouse models, db/db (UNx-high salt [HS] db/db), and their lean control, db/m ...
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A high amount of salt in the diet increases blood pressure (BP) and leads to salt-sensitive hypertension in individuals with impaired renal sodium excretion. Small guanosine triphosphatase (GTP)ase Rho and Rac, activated by salt intake, play important roles in the pathogenesis of salt-sensitive hypertension as key switches of intracellular signaling. Focusing on Rho, high salt intake in the central nervous system increases sodium concentrations of cerebrospinal fluid in salt-sensitive subjects v...
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#1Wakako Kawarazaki (UTokyo: University of Tokyo)H-Index: 11
#2Toshiro Fujita (UTokyo: University of Tokyo)H-Index: 121
Dietary salt intake increases blood pressure (BP) but the salt sensitivity of BP differs between individuals. The interplay of ageing, genetics and environmental factors, including malnutrition and stress, contributes to BP salt sensitivity. In adults, obesity is often associated with salt-sensitive hypertension. The children of women who experience malnutrition during pregnancy are at increased risk of developing obesity, diabetes and salt-sensitive hypertension as adults. Similarly, the offspr...
2 CitationsSource
#1Hajimu Kurumatani (Toray Industries)H-Index: 7
#2Kiyonobu Okada (Toray Industries)H-Index: 3
Last. Hidetomo Nakamoto (Saitama Medical University)H-Index: 31
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We conducted a multicenter, randomized, double-blind, placebo-controlled, phase IIb/III study (CASSIOPEIR) using a renal composite endpoint (i.e., doubling of SCr or end-stage renal disease) in seven Asian countries/region. CASSIOPEIR compared TRK-100STP (120 μg and 240 μg) with placebo in patients with non-diabetic CKD patients with primary glomerular disease or nephrosclerosis (n = 892). However, the superiority of TRK-100STP over placebo was not observed. A prior phase II study on which the P...
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#1Nobuhiro Ayuzawa (UTokyo: University of Tokyo)H-Index: 11
#2Toshiro Fujita (UTokyo: University of Tokyo)H-Index: 121
Hypertension and its comorbidities pose a major public health problem associated with disease-associated factors related to a modern lifestyle, such high salt intake or obesity. Accumulating evidence has demonstrated that aldosterone and its receptor, the mineralocorticoid receptor (MR), have crucial roles in the development of salt-sensitive hypertension and coexisting cardiovascular and renal injuries. Accordingly, clinical trials have repetitively shown the promising effects of MR blockers in...
1 CitationsSource
#1Takeshi MarumoH-Index: 17
#2Junichi HoshinoH-Index: 24
Last. Toshiro Fujita (UTokyo: University of Tokyo)H-Index: 121
view all 17 authors...
Introduction Renal tubular injury contributes to the decline in kidney function in patients with diabetes. Cell type-specific DNA methylation patterns have been used to calculate proportions of particular cell types. In this study, we developed a method to detect renal tubular injury in patients with diabetes by detecting exfoliated tubular cells shed into the urine based on tubular cell-specific DNA methylation patterns. Research design and methods We identified DNA methylation patterns specifi...
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#1Wakako Kawarazaki (UTokyo: University of Tokyo)H-Index: 11
#2Risuke Mizuno (UTokyo: University of Tokyo)H-Index: 6
Last. Toshiro Fujita (UTokyo: University of Tokyo)H-Index: 121
view all 10 authors...
Aging is associated with a high prevalence of hypertension due to elevated susceptibility of BP to dietary salt, but its mechanism is unknown. Serum levels of Klotho, an anti-aging factor, decline with age. We found that high salt (HS) increased BP in aged mice and young heterozygous Klotho-knockout mice and was associated with increased vascular expression of Wnt5a and p-MYPT1, which indicate RhoA activity. Not only the Wnt inhibitor LGK974 and the Wnt5a antagonist Box5 but Klotho supplementati...
7 CitationsSource
#1Conghui Wang (UTokyo: University of Tokyo)H-Index: 1
#1Conghui Wang (Chinese PLA General Hospital)H-Index: 1
Last. Tatsuo Shimosawa (International University of Health and Welfare)H-Index: 33
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Abstract To investigate the cause of salt sensitivity in a normotensive animal model, we treated rats with a low-dose of the nitric oxide synthase inhibitor, L-NAME, that does not elevate blood pressure per se or induce kidney fibrosis. A high salt diet increased the circulating blood volume both in L-NAME-treated and nontreated animals for the first 24 hours. Thereafter, the blood volume increase persisted only in the L-NAME-treated rats. Blood pressure was higher in the L-NAME-treated group fr...
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#1Daigoro Hirohama (UTokyo: University of Tokyo)H-Index: 11
#2Wakako Kawarazaki (UTokyo: University of Tokyo)H-Index: 11
Last. Toshiro Fujita (UTokyo: University of Tokyo)H-Index: 121
view all 7 authors...
Renal inflammation is known to be involved in salt-induced renal damage, leading to end-stage renal disease. This study aims to evaluate the role of inflammation in anti-inflammatory and renoprotective effects of beraprost sodium (BPS), a prostaglandin I2 (PGI2) analog, in Dahl salt-sensitive (DS) rats. Five-week-old male DS rats were fed a normal-salt diet (0.5% NaCl), a high-salt diet (8% NaCl), or a high-salt diet plus BPS treatment for 3 weeks. BPS treatment could inhibit marked proteinuria ...
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#1Nobuhiro Ayuzawa (UTokyo: University of Tokyo)H-Index: 11
#2Mitsuhiro Nishimoto (UTokyo: University of Tokyo)H-Index: 9
Last. Toshiro Fujita (UTokyo: University of Tokyo)H-Index: 121
view all 8 authors...
BACKGROUND: Regulation of sodium chloride transport in the aldosterone-sensitive distal nephron is essential for fluid homeostasis and BP control. The chloride-bicarbonate exchanger pendrin in beta-intercalated cells, along with sodium chloride cotransporter (NCC) in distal convoluted tubules, complementarily regulate sodium chloride handling, which is controlled by the renin-angiotensin-aldosterone system. METHODS: Using mice with mineralocorticoid receptor deletion in intercalated cells, we ex...
3 CitationsSource