研究者業績

田中 更沙

タナカ サラサ  (Sarasa Tanaka)

基本情報

所属
兵庫県立大学 環境人間学部 食環境栄養課程 助教
学位
博士(栄養学)(2013年3月)

J-GLOBAL ID
202001018798806567
researchmap会員ID
R000000447

研究キーワード

 1

論文

 23
  • Sarasa Tanaka, Hiromi Kawamura, Yumeno Imoto, Yuri Urata, Sayuka Hontama, Momoko Oda, Motoyoshi Sakaue, Mikiko Ito
    Journal of clinical biochemistry and nutrition 72(2) 126-131 2023年3月  
    Refeeding syndrome is a major clinical problem that leads to fatal complications in patients suffering from malnutrition. Hypophosphatemia inevitably is observed at the onset of refeeding syndrome and therefore is monitored during refeeding; however, the causes of metabolic changes in phosphate concentration during refeeding remain poorly understood. In a previous study, we established a refeeding syndrome model employing total parenteral nutrition with insulin-induced hypophosphatemia, but the symptoms were severe and the metabolic mechanisms in this model may not have been representative of clinical conditions. Therefore, we established a new animal model of mild refeeding syndrome by using a shorter fasting period followed by a single refeeding. These mild refeeding syndrome-model rats exhibited hypophosphatemia without increases in urinary phosphate excretion. Interestingly, administration of the combination of phosphate and insulin during refeeding promoted insulin secretion during refeeding. This model implies that Pi may directly promote insulin secretion in pancreatic cells. These results clarify the interaction between phosphate and glucose metabolism pancreatic cells during refeeding syndrome in a mild refeeding syndrome model.
  • Naoko Suga, Akira Murakami, Hideyuki Arimitsu, Kazuya Shiogama, Sarasa Tanaka, Mikiko Ito, Yoji Kato
    Journal of clinical biochemistry and nutrition 69(1) 61-67 2021年7月  
    Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, are chronic inflammatory disorders associated with oxidative stress. The intestines produce 5-hydroxytryptamine that may negatively affect disease state under inflammatory conditions when overproduced. 5-Hydroxytryptamine is a substrate for myeloperoxidase and is converted into reactive tryptamine-4,5-dione. Here, an experimental colitis model was established through oral administration of 5% dextran sulfate sodium to ICR mice for 7 days. Furthermore, the formation of tryptamine-4,5-dione in the colorectal mucosa/submucosa and colorectal tissue was analyzed by chemical and immunochemical methodologies. First, free tryptamine-4,5-dione in the homogenate was chemically trapped by o-phenylenediamine and analyzed as the stable phenazine derivative. Tryptamine-4,5-dione localization as adducted proteins in the colorectal tissue was immunohistochemically confirmed, and as demonstrated by both methods, this resulted in the significant increase of tryptamine-4,5-dione in dextran sulfate sodium-challenged mice compared with control mice. Immunohistochemical staining confirmed tryptamine-4,5-dione-positive staining at the myeloperoxidase accumulation site in dextran sulfate sodium-challenged mice colorectal tissue. The tryptamine-4,5-dione locus in the mice was partly matched with that of a specific marker for myeloperoxidase, halogenated tyrosine. Overall, the results possibly indicate that tryptamine-4,5-dione is generated by neutrophil myeloperoxidase in inflammatory tissue and may contribute to the development of inflammatory bowel disease.
  • Mariko Tani, Sarasa Tanaka, Chihiro Oeda, Yuichi Azumi, Hiromi Kawamura, Motoyoshi Sakaue, Mikiko Ito
    Journal of clinical biochemistry and nutrition 68(1) 23-31 2021年1月  
    Vascular calcification is major source of cardiovascular disease in patients with chronic kidney disease. Hyperphosphatemia leads to increased intracellular phosphorus influx, which leads to an increase in osteoblast-like cells in vascular smooth muscle cell. PiT-1 transports phosphate in vascular smooth muscle cell. However, the mechanism of vascular calcification is not completely understood. This study investigated candidate phosphorus-related molecules other than PiT-1. We hypothesized that phosphorus-related molecules belonging to the solute-carrier (SLC) superfamily would be involved in vascular calcification. As a result of DNA microarray analysis, we focused on SLC37A2 and showed that mRNA expression of these cells increased on calcified aotic smooth muscle cells (AoSMC). SLC37A2 has been reported to transport both glucose-6-phosphate/phosphate and phosphate/phosphate exchanges. In vitro analysis showed that SLC37A2 expression was not affected by inflammation on AoSMC. The expression of SLC37A2 mRNA and protein increased in calcified AoSMC. In vivo analysis showed that SLC37A2 mRNA expression in the aorta of chronic kidney disease rats was correlated with osteogenic marker genes. Furthermore, SLC37A2 was expressed at the vascular calcification area in chronic kidney disease rats. As a result, we showed that SLC37A2 is one of the molecules that increase with vascular calcification in vitro and in vivo.
  • Mariko Tani, Sarasa Tanaka, Kana Takamiya, Yoji Kato, Gaku Harata, Fang He, Motoyoshi Sakaue, Mikiko Ito
    Journal of clinical biochemistry and nutrition 67(3) 283-289 2020年11月  査読有り
    Vascular calcification progresses under hyperphosphatemia, and represents a risk factor for cardiovascular disease in chronic kidney disease (CKD) patients. We recently indicated that phosphorus (P) fluctuations also exacerbated vascular calcification in early-stage CKD rats. Dietary fiber intake is reportedly associated with cardiovascular risk. This study investigated the effects of dietary fiber on vascular calcification by repeated P fluctuations in early-stage CKD rats. Unilateral nephrectomy rats were used as an early-stage CKD model. For 36 days, a P fluctuation (LH) group was fed low-P (0.02% P) and high-P (1.2% P) diets alternating every 2 days, and a P fluctuation with dietary fiber intake (LH + F) group was fed low-P and high-P diets containing dietary fiber alternating every 2 days. The effect on vascular calcification was measured calcium content. Effects on uremic toxin were measured levels of indoxyl sulfate (IS) and investigated gut microbiota. The LH + F group showed significantly reduced vessel calcium content compared to the LH group. Further, dietary fiber inhibited increases in blood levels of IS after intake of high-P diet, and decreased uremic toxin-producing intestinal bacteria. Dietary fiber may help suppress progression of vascular calcification due to repeated P fluctuations in early-stage CKD rats by decreasing uremic toxin-producing intestinal bacteria.
  • Keisuke Kawamoto, Masae Sakuma, Sarasa Tanaka, Masashi Masuda, Mari Nakao-Muraoka, Yuki Niida, Yurino Nakamatsu, Mikiko Ito, Yutaka Taketani, Hidekazu Arai
    Nutrition (Burbank, Los Angeles County, Calif.) 72 110694-110694 2020年4月  査読有り
    OBJECTIVE: The ratio of dietary carbohydrate to fat may affect phosphorus metabolism because both calcium and phosphorus are regulated by similar metabolic mechanisms, and a high-fat diet (HFD) induces deleterious effects on the absorption of dietary calcium. We hypothesized that an HFD induces an increase in phosphorus absorption. The aim of this study was to evaluate the effects of differences in the quantity and quality of dietary fat on phosphorus metabolism over the short- and long-term. METHODS: Eighteen 8-wk-old Sprague-Dawley male rats were fed an isocaloric diet containing varied ratios of carbohydrates to fat energy and sources of fat (control diet, HFD, and high- saturated fat diet [HF-SFA]). At 3 d and 7 wk after the allocation and initiation of the test diets, feces and urine were collected and used for phosphorus and calcium measurement. RESULTS: The fecal phosphorous concentration (F-Pi) was lower in the HF-SFA group than in the other two groups; however, the urine phosphorus concentration (U-Pi) was significantly higher in the HF-SFA group than the other two groups when the rats were fed over the short- (P < 0.01) and long -term (P < 0.01 versus control, P < 0.05 versus HFD group). There were no significant differences in type-IIa sodium-phosphate cotransporter (NaPi-2 a) and type-IIc sodium-phosphate cotransporter (NaPi-2 c) mRNA expression, which are renal phosphate transport-related genes; however, the expression of type-IIb sodium-phosphate cotransporter (NaPi-2 b) and type-III sodium-phosphate cotransporter (Pit-1) mRNA in the duodenum was higher in the HFD and HF-SFA groups than in the control group (P < 0.05), although there were no significant differences in these in the jejunum. CONCLUSIONS: The present results indicated that an HFD, particularly HF-SFA, increases intestinal phosphate absorption compared with control.
  • Mariko Tani, Sarasa Tanaka, Kana Takamiya, Motoyoshi Sakaue, Mikiko Ito
    Journal of clinical biochemistry and nutrition 66(2) 139-145 2020年3月  
    Cardiovascular disease is a major cause of death among hemodialysis patients. Hyperphosphatemia induces cardiovascular disease through vascular endothelial dysfunction and calcification. Repetition of a short-term excessive-phosphorus (P) diet causes transient elevations in plasma P and subsequent vascular endothelial dysfunction in normal rats. The purpose of this study was to investigate the effects of the P fluctuation on vascular calcification and inflammation in rats after unilateral nephrectomy as an early-stage chronic kidney disease (CKD) model. Rats were bred for 36 days; CP group, fed a control P (0.6%) diet; HP group, fed a high-P (1.2%) diet; and P fluctuation group, fed low-P (0.02%) and high-P diets alternately every 2 days. Influences on vascular calcification were analyzed using Von Kossa staining and measurement of vessel Ca content. The influence on inflammation was measured as urinary levels of 8-hydroxy-2'-deoxyguanosine. We demonstrated that the P fluctuation group showed similar vascular calcification and inflammation to the HP group, despite having the same total P intake as the CP group. A diet avoiding P fluctuations may be important for patients with early-stage CKD.
  • 河村弘美, 阪上詩織, 田中更沙, 松井麻有, 谷真理子, 石谷翠里, 坂上元祥, 伊藤美紀子
    日本病態栄養学会誌 21(4) 495-503 2018年12月  査読有り
  • Hiromi Kawamura, Sarasa Tanaka, Yuri Ota, Sumire Endo, Mariko Tani, Midori Ishitani, Motoyoshi Sakaue, Mikiko Ito
    Journal of clinical biochemistry and nutrition 62(2) 167-173 2018年3月  査読有り
    Phosphorus management through dietetic therapy is vital for the prevention of cardiovascular disease in chronic kidney disease patients. There are two main sources of phosphorus in the diet, organic phosphorus from protein and inorganic phosphorus from food additives. The adverse effects of high phosphorus intake on vascular-endothelium function have been reported; however, the differences in the effects of organic phosphorus versus inorganic phosphorus are not clear. In this study, we examined an acute effect of these high phosphorus meals intake on vascular-endothelium function. This was a randomized, double-blind, cross-over test study design targeting healthy young men. We conducted a food intake test using two test meals, one high in organic phosphorus from organic food sources, and one high in inorganic phosphorus from food additives. Endothelium-dependent vasodilation, phosphorus and calcium in the urine and blood, and phosphorus-related hormones were measured preprandial to 120 min postprandial. The results showed higher serum and urine phosphorus values after the high inorganic phosphorus meal, and a significant reduction in endothelium-dependent vasodilation at 30 min postprandial. These findings are evidence that inorganic phosphorus has a stronger influence on vascular-endothelium function than organic phosphorus.
  • Hiromi Kawamura, Sarasa Tanaka, Yuri Uenami, Mariko Tani, Midori Ishitani, Saeko Morii, Motoyoshi Sakaue, Mikiko Ito
    The journal of medical investigation : JMI 65(1.2) 50-55 2018年  査読有り
    Refeeding syndrome (RFS) is characterized by the metabolic and clinical changes that occur following aggressive nutritional supplementation in malnourished patients. Hypophosphatemia is the hallmark of RFS and is key to its prevention and treatment in clinical practice. However, the mechanism of hypophosphatemia during RFS is unclear because of the lack of an animal model. In this study, we developed a rat RFS model as a first step to clarifying the molecular mechanism. After establishing the parenteral route, rats were fasted for 5 days and refeeding was started using total parenteral nutrition. The animals were infused with a high calorie solution with or without insulin administration. Results showed that plasma phosphate levels did not decrease in rats infused with the high calorie solution alone;in contrast, a 20% reduction compared to baseline was observed in rats administered insulin. In addition, rats infused with the high calorie solution containing added phosphate did not present with hypophosphatemia. Thus, we developed a rat RFS model with hypophosphatemia by tube feeding and insulin administration, and demonstrated the importance of phosphate in preventing refeeding hypophosphatemia. J. Med. Invest. 65:50-55, February, 2018.
  • Mikiko Ito, Sarasa Tanaka
    Clinical calcium 26(3) 375-83 2016年3月  
    The nutrition is important for prevention and improvement in bone disorder. Especially osteoporosis associated with nutrition. It has entered the super-aged society in 2007, a further increase in osteoporosis patients are concerned in Japan. Many studies have shown that associated with calcium, vitamin D, vitamin K intake and bone density and fracture. Relationship of osteoporosis and nutrition, despite the general awareness is high, calcium intake is not at all reached the achievement to recommend dietary allowance. In addition, vitamin D deficiency rickets in children, which has been considered in the past of the disorder, there is an increasing trend from such exposure shortage to the infancy of sunlight, vitamin D deficiency in pregnant women, the recommended breastfeeding. Improvement of lifestyle and diet from young age is important for bone disorder prevention.
  • Sarasa Tanaka, Mikiko Ito
    Clinical calcium 25(7) 1057-62 2015年7月  
    Renal osteodystrophy is the damage of bone morphology by CKD and treatment and occurred abnormal bone metabolism through renal dysfunction. It demonstrated that the control of P and Ca improves to normalization of mineral metabolism. Protein energy wasting and malnutrition are common in patients with CKD stage 5 and has been associated with life prognosis. In CKD patients, nutritional management is a critical role of treatment. Also it may be important of nutritional management that control P and Ca and improve nutritional status in renal osteodystrophy patients.
  • Shoko Ikeda, Hironori Yamamoto, Masashi Masuda, Yuichiro Takei, Otoki Nakahashi, Mina Kozai, Sarasa Tanaka, Mari Nakao, Yutaka Taketani, Hiroko Segawa, Masayuki Iwano, Ken-ichi Miyamoto, Eiji Takeda
    American journal of physiology. Renal physiology 306(7) F744-50 2014年4月1日  査読有り
    The type IIa sodium-dependent phosphate cotransporter (Npt2a) plays a critical role in reabsorption of inorganic phosphate (Pi) by renal proximal tubular cells. Pi abnormalities during early stages of sepsis have been reported, but the mechanisms regulating Pi homeostasis during acute inflammation are poorly understood. We examined the regulation of Pi metabolism and renal Npt2a expression during lipopolysaccharide (LPS)-induced inflammation in mice. Dose-response and time-course studies with LPS showed significant increases of plasma Pi and intact parathyroid hormone (iPTH) levels and renal Pi excretion, while renal calcium excretion was significantly decreased. There was no difference in plasma 1,25-dihydroxyvitamin D levels, but the induction of plasma intact fibroblast growth factor 23 levels peaked 3 h after LPS treatment. Western blotting, immunostaining, and quantitative real-time PCR showed that LPS administration significantly decreased Npt2a protein expression in the brush border membrane (BBM) 3 h after injection, but there was no change in renal Npt2a mRNA levels. Moreover, tumor necrosis factor-α injection also increased plasma iPTH and decreased renal BBM Npt2a expression. Importantly, we revealed that parathyroidectomized rats had impaired renal Pi excretion and BBM Npt2a expression in response to LPS. These results suggest that the downregulation of Npt2a expression in renal BBM through induction of plasma iPTH levels alter Pi homeostasis during LPS-induced acute inflammation.
  • Otoki Nakahashi, Hironori Yamamoto, Sarasa Tanaka, Mina Kozai, Yuichiro Takei, Masashi Masuda, Ichiro Kaneko, Yutaka Taketani, Masayuki Iwano, Ken-Ichi Miyamoto, Eiji Takeda
    Journal of clinical biochemistry and nutrition 54(2) 102-8 2014年3月  査読有り
    Members of the fibroblast growth factor (FGF) 19 subfamily, including FGF23, FGF15/19, and FGF21, have a role as endocrine factors which influence the metabolism of inorganic phosphate (Pi) and vitamin D, bile acid, and energy. It has been reported that dietary Pi regulates circulating FGF23. In this study, the short-term effects of dietary Pi restriction on the expression of FGF19 subfamily members in mice were analyzed. An initial analysis confirmed plasma FGF23 levels positively correlated with the amount of dietary Pi. On the other hand, ileal Fgf15 gene expression, but not hepatic Fgf21 gene expression, was up-regulated by dietary Pi restriction. In addition, we observed the increase of plasma 1,25-dihydroxyvitamin D [1,25(OH)2D] levels by dietary Pi restriction, and the up-regulation of ileal Fgf15 mRNA expression by 1,25(OH)2D3 and vitamin D receptor (VDR). Importantly, dietary Pi restriction-induced Fgf15 gene expression was prevented in VDR-knockout mice. Furthermore, diurnal variations of plasma triglyceride concentrations and hepatic mRNA expression of the bile acid synthesis enzyme Cyp7a1 as one of Fgf15 negative target genes was influenced by dietary Pi restriction. These results suggest that dietary Pi restriction up-regulates ileal Fgf15 gene expression through 1,25(OH)2D3 and VDR, and may affect hepatic bile acid homeostasis.
  • 山本 浩範, 竹井 悠一郎, 香西 美奈, 田中 更沙, 坂本 達昭, 池田 涼子
    ビタミン 87(9) 514-518 2013年9月  
    ビタミンDは、内分泌ホルモンとして骨およびカルシウム恒常性の制御の中心的役割を担っている。ビタミンD受容体の役割と遺伝子変異、ビタミンD受容体遺伝子多型と骨密度、ビタミンD受容体遺伝子多型と骨粗鬆症予防、VDR遺伝子多型と食品摂取および運動について述べた。
  • Sarasa Tanaka, Hironori Yamamoto, Otoki Nakahashi, Tomohiro Kagawa, Mariko Ishiguro, Masashi Masuda, Mina Kozai, Shoko Ikeda, Yutaka Taketani, Eiji Takeda
    Nutrition research (New York, N.Y.) 33(7) 586-93 2013年7月  査読有り
    Excessive inorganic phosphate (Pi) intake and hyperphosphatemia have both been speculated to be risk factors for cardiovascular disease and hypercholesterolemia, and dysregulation of cholesterol metabolism can lead to atherosclerosis. However, the relationship between Pi and cholesterol metabolism has not been investigated in detail. Our recent study showed that triiodothyronine can induce both hyperphosphatemia and hypocholesterolemia in mice. We therefore hypothesized a possible linkage between Pi and cholesterol metabolism. In this study, we investigated the effects of dietary Pi intake on cholesterol metabolism in mice. Mice were divided into 4 groups, which were fed diets containing 1.2% or 0.1% Pi and with or without 2% cholesterol (Pi-sufficient, Pi-restricted, Pi-sufficient + Chol, and Pi-restricted + Chol), for 12 days. Inorganic phosphate-restricted mice exhibited significantly higher liver weights than did Pi-sufficient mice. Interestingly, dietary Pi restriction significantly increased high-cholesterol diet-induced hepatic lipid accumulation. Real-time polymerase chain reaction analysis revealed that dietary Pi restriction decreased expression of hepatic genes involved in cholesterol metabolism and fatty acid biosynthesis. In addition, hepatic messenger RNA levels of several transcription factors including peroxisome proliferator-activated receptors and liver X receptor were markedly decreased by Pi restriction. Furthermore, plasma lipid and lipoprotein profile analysis showed that dietary Pi restriction reduced susceptibility to high-cholesterol diet-induced hyperlipidemia. Importantly, we found that there was a significant negative correlation between plasma levels of Pi and total cholesterol. These results suggest that dietary Pi plays an important role in the development of fatty liver disease and hyperlipidemia induced by a high-cholesterol diet through regulation of lipid metabolism-related gene expression in the liver.
  • Sarasa Tanaka, Hironori Yamamoto, Otoki Nakahashi, Mariko Ishiguro, Yuichiro Takei, Masashi Masuda, Mina Kozai, Shoko Ikeda, Yutaka Taketani, Ken-ichi Miyamoto, Eiji Takeda
    The journal of medical investigation : JMI 60(3-4) 191-6 2013年  査読有り
    The type IIa sodium-dependent phosphate co-transporter (Npt2a) is important to maintain renal inorganic phosphate (Pi) homeostasis and the plasma Pi levels. It has reported that disorder of Pi metabolism in kidney can be risk factors for cardiovascular disease as well as hypercholesterolemia. However, the relationship between Pi and cholesterol metabolism has not been clarified. The current study investigated the effects of Npt2a gene ablation that is known as hypophosphatemia model on cholesterol metabolism in mice. Npt2a deficient (Npt2a(-/-)) mice and wild type mice were fed diets with or without 2% cholesterol for 12 days. Plasma lipid and lipoprotein profile analysis revealed that plasma lipid levels (total, LDL and HDL cholesterol) were significantly higher in Npt2a(-/-) mice than wild type (WT) mice. Interestingly, high cholesterol diet markedly increased plasma levels of total, LDL and HDL cholesterol in WT mice, but not Npt2a(-/-) mice. On the other hand, there were no differences in body and liver weight, intake and hepatic lipid accumulation between WT and Npt2a(-/-) mice. These results suggest that ablation of Npt2a gene induces hypercholesterolemia and affects the ability to respond normally to dietary cholesterol.
  • Takashi Uebanso, Yutaka Taketani, Hironori Yamamoto, Kikuko Amo, Sarasa Tanaka, Hidekazu Arai, Yuichiro Takei, Masashi Masuda, Hisami Yamanaka-Okumura, Eiji Takeda
    The Journal of nutritional biochemistry 23(7) 785-90 2012年7月  査読有り
    Cholesterol homeostasis is regulated by the liver X receptor (LXR) at the transcriptional level, but it remains unknown whether LXR can affect expression levels of intrahepatic lipolysis related gene. Recent evidence has demonstrated that fibroblast growth factor 21 (FGF21) regulates hepatic lipolysis and fatty acid utilization. In the present study, we examined the role of LXR in FGF21 gene expression associated with regulation of cross-talk signals between cholesterol and triglyceride metabolism in the liver. An in vivo cholesterol feeding test revealed that intake of excess cholesterol increased cholesterol catabolism related gene expression as well as fatty-acid biosynthesis related gene expression. Moreover, the accumulated cholesterol suppressed FGF21 and hormone-sensitive lipase (HSL) gene expression. After 15-day cholesterol feeding, hepatic triglyceride concentrations were negatively correlated with expression levels of the FGF21 and HSL genes in the liver. An LXR agonist (TO-901317) repressed the FGF21 gene expression in mouse primary hepatocytes and HepG2 cells. A promoter deletion study and electrophoretic mobility shift assay revealed that the human FGF21 promoter has at least one LXR response element located from -37 to -22 bp. In summary, LXR represses FGF21 gene expression at the transcription level and might suppress lipolysis and lipid utilization to protect the liver from excess accumulation of toxic cholesterol.
  • Nguyen Trong Hung, Hironori Yamamoto, Yuichiro Takei, Masashi Masuda, Ayako Otani, Mina Kozai, Shoko Ikeda, Otoki Nakahashi, Sarasa Tanaka, Yutaka Taketani, Eiji Takeda
    Journal of clinical biochemistry and nutrition 50(3) 227-33 2012年5月  査読有り
    Stanniocalcin 1 and stanniocalcin 2 are two glycoprotein hormones, which act as calcium phosphate-regulating factor on intestine and kidney. We have previously reported that stanniocalcin 2 expression is positively and negatively controlled by 1,25(OH)(2)D(3) and parathyroid hormone in renal proximal tubular cells. However, it has been unclear whether they regulate the stanniocalcin 1 gene expression. In this study, we identified the opossum stanniocalcin 1 cDNA sequence. The opossum stanniocalcin 1 amino acid sequence had 83% homology with human stanniocalcin 1, and has a conserved putative N-linked glycosylation site. Real-time PCR analysis using opossum kidney proximal tubular (OK-P) cells revealed that the mRNA levels of stanniocalcin 1 gene is up-regulated by both 1,25(OH)(2)D(3) and parathyroid hormone in dose-dependent and time-dependent manners. We also demonstrated that the stanniocalcin 1 expression was increased in parathyroid hormone injected rat kidney. Furthermore, the mRNA expression of stanniocalcin 1 and stanniocalcin 2 were oppositely regulated by phorbol 12,13-myristic acetate, a specific PKC activator. Interestingly, the up-regulation of stanniocalcin 1 gene by 1,25(OH)(2)D(3) and phorbol 12,13-myristic acetate were not prevented in the presence of actinomycin D, an RNA synthesis inhibitor. These results suggest that the stanniocalcin 1 gene expression is up-regulated by 1,25(OH)(2)D(3) and parathyroid hormone through mRNA stabilization in renal proximal tubular cells.
  • Masashi Masuda, Hironori Yamamoto, Mina Kozai, Sarasa Tanaka, Mariko Ishiguro, Yuichiro Takei, Otoki Nakahashi, Shoko Ikeda, Takashi Uebanso, Yutaka Taketani, Hiroko Segawa, Ken-ichi Miyamoto, Eiji Takeda
    The Biochemical journal 429(3) 583-92 2010年8月1日  査読有り
    The type II sodium-dependent phosphate co-transporters Npt2a and Npt2c play critical roles in the reabsorption of Pi by renal proximal tubular cells. The vitamin A metabolite ATRA (all-trans-retinoic acid) is important for development, cell proliferation and differentiation, and bone formation. It has been reported that ATRA increases the rate of Pi transport in renal proximal tubular cells. However, the molecular mechanism is still unknown. In the present study, we observed the effects of a VAD (vitamin A-deficient) diet on Pi homoeostasis and the expression of Npt2a and Npt2c genes in rat kidney. There was no change in the plasma levels of Pi, but VAD rats significantly increased renal Pi excretion. Renal brush-border membrane Pi uptake activity and renal Npt2a and Npt2c expressions were significantly decreased in VAD rats. The transcriptional activity of a luciferase reporter plasmid containing the promoter region of human Npt2a and Npt2c genes was increased markedly by ATRA and a RAR (retinoic acid receptor)-specific analogue TTNPB {4-[E-2-(5,6,7,8-tetrahydro-5,5,8,8-tetra-methyl-2-naphtalenyl)-1-propenyl] benzoic acid} in renal proximal tubular cells overexpressing RARs and RXRs (retinoid X receptors). Furthermore, we identified RAREs (retinoic acid-response elements) in both gene promoters. Interestingly, the half-site sequences (5'-GGTTCA-3': -563 to -558) of 2c-RARE1 overlapped the vitamin D-responsive element in the human Npt2c gene and were functionally important motifs for transcriptional regulation of human Npt2c by ATRA and 1,25(OH)2D3 (1alpha,25-dihydroxyvitamin D3), in both independent or additive actions. In summary, we conclude that VAD induces hyperphosphaturia through the down-regulation of Npt2a and Npt2c gene expression in the kidney.
  • 中橋 乙起, 山本 浩範, 池田 翔子, 田中 更沙, 竹井 悠一郎, 竹谷 豊, 宮本 賢一, 加藤 茂明, 武田 英二
    ビタミン 84(4) 173-173 2010年4月  
  • Mariko Ishiguro, Hironori Yamamoto, Masashi Masuda, Mina Kozai, Yuichiro Takei, Sarasa Tanaka, Tadatoshi Sato, Hiroko Segawa, Yutaka Taketani, Hidekazu Arai, Ken-Ichi Miyamoto, Eiji Takeda
    The Biochemical journal 427(1) 161-9 2010年3月15日  査読有り
    The type IIa renal sodium-dependent phosphate (Na/Pi) co-transporter Npt2a is implicated in the control of serum phosphate levels. It has been demonstrated previously that renal Npt2a protein and its mRNA expression are both up-regulated by the thyroid hormone T3 (3,3',5-tri-iodothyronine) in rats. However, it has never been established whether the induction was mediated by a direct effect of thyroid hormones on the Npt2a promoter. To address the role of Npt2a in T3-dependent regulation of phosphate homoeostasis and to identify the molecular mechanisms by which thyroid hormones modulate Npt2a gene expression, mice were rendered pharmacologically hypo- and hyper-thyroid. Hypothyroid mice showed low levels of serum phosphate and a marked decrease in renal Npt2a protein abundance. Importantly, we also showed that Npt2a-deficient mice had impaired serum phosphate responsiveness to T3 compared with wild-type mice. Promoter analysis with a luciferase assay revealed that the transcriptional activity of a reporter gene containing the Npt2a promoter and intron 1 was dependent upon TRs (thyroid hormone receptors) and specifically increased by T3 in renal cells. Deletion analysis and EMSAs (electrophoretic mobility-shift assays) determined that there were unique TREs (thyroid-hormone-responsive elements) within intron 1 of the Npt2a gene. These results suggest that Npt2a plays a critical role as a T3-target gene, to control phosphate homoeostasis, and that T3 transcriptionally activates the Npt2a gene via TRs in a renal cell-specific manner.
  • 浦川 千鶴, 山本 浩範, 竹井 悠一郎, 田中 更沙, 菊地 浩子, 竹谷 豊, 武田 英二
    日本栄養・食糧学会大会講演要旨集 63回 216-216 2009年5月  
  • 浦川 千鶴, 山本 浩範, 竹井 悠一郎, 田中 更沙, 菊地 浩子, 竹谷 豊, 武田 英二
    日本病態栄養学会誌 11(5) 138-138 2008年12月  

MISC

 8
  • 山本 浩範, 石黒 真理子, 福田 詩織, 中橋 乙起, 田中 更沙, 増田 真志, 武田 英二, 竹谷 豊
    四国医学雑誌 79(5-6) 209-214 2024年3月  
  • 金子一郎, 田中更沙
    Phosphorus Letter (108) 2023年  
  • 山本 浩範, 石黒 真理子, 田中 更沙, 竹井 悠一郎, 増田 真志, 大西 康太, 竹谷 豊
    ビタミン 94(4) 246-246 2020年4月  
  • 伊藤 美紀子, 田中 更沙
    Clinical Calcium 26(3) 375-383 2016年2月  
    骨粗鬆症をはじめとした骨疾患では、栄養や食習慣と深い関連があり、その予防ならびに改善において栄養を抜きにして考えることはできない。我が国は2007年に超高齢社会に突入しており、さらなる骨粗鬆症患者の増加が懸念されている。骨粗鬆症と栄養、特にカルシウムとの関係は一般の認知度が高いにもかかわらず、栄養摂取の目標達成には全く至っていない。また、過去の病気と思われていた小児のビタミンD欠乏性くる病が、妊産婦のビタミンD欠乏、母乳栄養の推奨、乳児期の日光への曝露不足などから増加傾向にある。骨疾患予防のためには若年期からの生活習慣・食生活の改善が重要である。(著者抄録)
  • 田中 更沙, 伊藤 美紀子
    Clinical Calcium 25(7) 1057-1062 2015年6月  
    腎性骨症は慢性腎臓病(CKD)またはその治療に伴い起こる骨組織障害の総称であり、腎機能の低下に伴うミネラル代謝異常により骨代謝に異常をきたす病態である。ミネラル代謝異常改善のため、P、Caの管理が重要であることが明らかとなっている。CKD患者における特徴的な栄養障害としてprotein-energy wasting(PEW)が知られており、生命予後と強く関連する。このようにCKD患者において食事療法は治療において大きな役割を占めており、腎性骨症においてもP、Caの管理および全身の栄養状態の改善に栄養管理は重要であると考えられる。(著者抄録)

講演・口頭発表等

 35

共同研究・競争的資金等の研究課題

 8