Mitsuhiro Nishimoto
University of Tokyo
GeneInternal medicineDownregulation and upregulationVesicleEndocrinologyEndoplasmic reticulumDNA demethylationLymphatic systemKnockout mouseChemistryMineralocorticoid receptorDNA methylationCameleon (protein)MineralocorticoidAlbuminuriaLymphangiogenesisInflammationPendrinAldosteroneKidney diseaseLymphDiabetic nephropathyEplerenoneKidneyExtracellularAngiotensin IIImmunoelectron microscopySalt intakeEpigeneticsSecretionCaveolaeCancer researchMedicineUrinary systemIntracellularBlood pressureBiologyCell biology
21Publications
9H-index
232Citations
Publications 20
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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#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
#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
#1Mitsuhiro Nishimoto (UTokyo: University of Tokyo)H-Index: 9
#2Hiroshi OhtsuH-Index: 12
Last. Toshiro Fujita (UTokyo: University of Tokyo)H-Index: 121
view all 14 authors...
Excessive dietary salt intake can counteract the renoprotective effects of renin–angiotensin system (RAS) blockade in hypertensive patients with chronic kidney disease (CKD). In rodents, salt loading induces hypertension and renal damage by activating the mineralocorticoid receptor (MR) independently of plasma aldosterone levels. Thus, high salt-induced resistance to RAS blockade may be mediated by MR activation. To test this, a post hoc analysis of the Eplerenone Combination Versus Conventional...
11 CitationsSource
#1Shigeyoshi Oba (UTokyo: University of Tokyo)H-Index: 14
#2Nobuhiro Ayuzawa (UTokyo: University of Tokyo)H-Index: 11
Last. Toshiro Fujita (UTokyo: University of Tokyo)H-Index: 121
view all 10 authors...
Epigenetic modulation may underlie the progression of diabetic nephropathy (DN). Involvement of TGFB1 in mesangial fibrosis of DN led us to hypothesize that Tgfb1 DNA demethylation contributes to progression of DN. In primary mesangial cells from diabetic (db/db) mouse kidneys, demethylation of Tgfb1 DNA and upregulation of Tgfb1 mRNA progressed simultaneously. USF1 binding site in Tgfb1 promoter region were demethylated, and binding of USF1 increased, with decreased binding of DNMT1 in db/db co...
9 CitationsSource
#1Fumiko Kawakami-Mori (UTokyo: University of Tokyo)H-Index: 9
#2Mitsuhiro Nishimoto (UTokyo: University of Tokyo)H-Index: 9
Last. Toshiro FujitaH-Index: 121
view all 12 authors...
: Maternal malnutrition, which causes prenatal exposure to excessive glucocorticoid, induces adverse metabolic programming, leading to hypertension in offspring. In offspring of pregnant rats receiving a low-protein diet or dexamethasone, a synthetic glucocorticoid, mRNA expression of angiotensin receptor type 1a (Agtr1a) in the paraventricular nucleus (PVN) of the hypothalamus was upregulated, concurrent with reduced expression of DNA methyltransferase 3a (Dnmt3a), reduced binding of DNMT3a to ...
10 CitationsSource
#1Mitsuhiro Nishimoto (UTokyo: University of Tokyo)H-Index: 9
#2Risuke Mizuno (UTokyo: University of Tokyo)H-Index: 6
Last. Masashi Isshiki (Saitama Medical University)H-Index: 15
view all 4 authors...
In vascular endothelial cells, store-operated calcium entry (SOCE) activates endothelial NO synthase (eNOS) and regulates nitric oxide (NO) production as well as flow-dependent mechanical stimuli. Stromal interaction molecule 1, or STIM1, was recently identified to be essential for SOCE, acting as a calcium sensor for intracellular calcium stores. However, how STIM1 affects endothelial function and blood pressure (BP) remains unclear. We generated STIM1 fl/fl mice and vascular endothelial cell-s...
6 CitationsSource
#1Atsushi Watanabe (National Defense Medical College)H-Index: 4
#1Atsushi Watanabe (National Defense Medical College)H-Index: 6
Last. Toshiro Fujita (UTokyo: University of Tokyo)H-Index: 121
view all 14 authors...
Epigenetic abnormalities have been suggested to mediate metabolic memory observed in diabetic complications. We have shown that epigenetic alterations may induce persistent phenotypic changes in the proximal tubules of the diabetic kidneys. In this study, we show that pregnane X receptor (PXR), a xenobiotic nuclear receptor, is epigenetically altered and upregulated, and may have a possible function in the diabetic kidney. PXR has been shown to play a critical role in metabolic changes in obesit...
7 CitationsSource