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From School 【 display / non-display 】
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Toyama Medical and Pharmaceutical University Faculty of Pharmaceutical Science Graduated
1995.04 - 1999.03
From Graduate School 【 display / non-display 】
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Kyoto University Graduate School, Division of Agriculture Doctoral program (second term) Completed
2016.04 - 2019.03
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Toyama Medical and Pharmaceutical University Graduate School, Division of Pharmaceutical Sciences Doctoral program (first term) Completed
1999.04 - 2001.03
Degree 【 display / non-display 】
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博士（農学） ( 2019.03 京都大学 )
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修士（薬学） ( 2001.03 富山医科薬科大学 )
Employment Record in Research 【 display / non-display 】
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Tokyo University of Agriculture Faculty of Applied Bio-Science Department of Nutritional Science and Food Safety Professor
2023.04
External Career 【 display / non-display 】
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日本たばこ産業株式会社 医薬総合研究所 主任研究員
2001.04 - 2023.03
Country：Japan
Professional Memberships 【 display / non-display 】
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日本安全性薬理研究会
2014.04
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日本毒性学会
2008.04
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日本薬理学会
2004.02
Research Areas 【 display / non-display 】
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Life Science / Laboratory animal science / Toxicology
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Life Science / Pharmacology / Safety Pharmacology
Papers 【 display / non-display 】
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High-cholesterol diet in combination with hydroxypropyl-β-cyclodextrin induces NASH-like disorders in the liver of rats. Reviewed
Saigo Y, Sasase T, Tohma M, Uno K, Shinozaki Y, Maekawa T, Sano R, Miyajima K, Ohta T.
Physiological Research 72 371 - 382 2023.06
Language：English Publishing type：Research paper (scientific journal)
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GPR52 Accelerates Fatty Acid Biosynthesis in a Ligand-dependent Manner in Hepatocytes and in Response to Excessive Fat Intake in Mice Reviewed
Wada M, Yukawa K, Ogasawara H, Suzawa K, Maekawa T, Yamamoto Y, Ohta T, Lee E, Miki T
iScience 24 2021.04
Language：English Publishing type：Research paper (scientific journal)
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Renal transcriptome analysis of uninephrectomized db/db mice identified a mechanism for the transition to severe diabetic nephropathy Reviewed
Maekawa M, Maekawa T, Sasase T, Wakashima T, Uemura A, Uno K, Ohta T, Yamada T.
Experimental Animals 73 ( 1 ) 29 - 40 2024.02
Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)
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Effects of salt supplementation in uninephrectomized KK-Ay mice: Examining the potential of a diabetic kidney disease model Reviewed
Sano R, Ryu K, Sasase T, Shinozaki Y, Teoh SH, Yamaguchi A, Uno K, Maekawa T, Ohta T, Miyajima K.
The Journal of Toxicological Sciences 48 ( 11 ) 597 - 606 2023.11
Language：English Publishing type：Research paper (scientific journal)
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Establishment of a new nonalcoholic steatohepatitis model; Ovariectomy exacerbates nonalcoholic steatohepatitis-like pathology in diabetic rats Reviewed
Saigo Y, Sasase T, Uno K, Shinozaki Y, Maekawa T, Sano R, Toriniwa Y, Miyajima K, Ohta T
Journal of Pharmacological and Toxicological Methods 116 117190 2022.07
Language：English Publishing type：Research paper (scientific journal)
Presentations 【 display / non-display 】
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Utility of N-Titin as a skeletal muscle atrophy marker in a mouse model of skeletal muscle atrophy
RYOKE Katsunori, ISHIZUKA Kana, YASUI Yuzo, KONDO Kazuma, KEMURIYAMA Noriko, MAEKAWA Tatsuya, MIYAJIMA Katsuhiro
Annual Meeting of the Japanese Society of Toxicology 2024 The Japanese Society of Toxicology
Language：Japanese
<p>[Introduction] Titin is a large protein that is specifically expressed in striated muscle and essential for the maintenance of sarcomere structure. Recently, N-terminal fragment of the Titin (N-Titin) has been reported to show high levels in human urine in patients with muscular diseases and is expected to serve as a diagnostic biomarker for these diseases. In this study, we examined utility of N-titin as a biomarker to detect atrophy in mice with muscle atrophy. [Methods] Male BALB/c mice (6 weeks of age, n=5 per group) were given 10 mg/L dexamethasone (DEX) dissolved in drinking water for 4 weeks. During the treatment period, urine sample, collected before initiation of the treatment period and at Week 1, 2, 3 and 4 of the treatment period, were used for determination of urinary N-Titin/creatinine (CRN) concentration ratio. At the end of the treatment period, measurements of muscle weights and mRNA levels of genes associated with muscle atrophy (Atrogin-1 and MuRF-1), and histopathological examination were conducted. [Results/Discussion] Although there were no histopathological abnormalities in the gastrocnemius muscle (GAS), muscle fiber cross-sectional area was decreased after 4 weeks of DEX treatment. The GAS weight was significantly decreased and mRNA levels of Atrogin-1 and MuRF-1 in the GAS were both increased after 4 weeks of DEX treatment. Interestingly, urinary N-Titin/CRN ratio markedly increased from Week 2 of the DEX treatment. These results suggesting that the urinary N-Titin/CRN ratio could be a biomarker for monitoring skeletal muscle atrophy in mice.</p>
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Regulatory mechanism of phosphorus homeostasis in uninephrectomized mice fed a high phosphorus diet
KAGAMI Nodoka, SEKIGUCHI Keita, MITSUI Ayaka, KEMURIYAMA Noriko, MAEKAWA Tatsuya, MIYAJIMA Katsuhiro
Annual Meeting of the Japanese Society of Toxicology 2024 The Japanese Society of Toxicology
Language：Japanese
<p>[Objective] In this study, we fed potassium tripolyphosphate (K5P3O10) to uninephrectomized mice and investigated phosphorus homeostasis during renal injury.</p><p>[Materials and Methods] Six-week-old C57BL/6J mice underwent right uninephrectomy and were fed a diet containing 1.5% K5P3O10 for 4 or 8 weeks (high-P diet group). The control group (low-P diet group) and sham treatment group were fed a diet containing 0.3% K₅P₃O₁₀. After the feeding period, blood Ca and P concentrations were measured, and gene expression analysis of phosphate transporter-related genes (slc34a2a, slc34a2b, slc34a2c) in the kidney and small intestine and vitamin D hydroxylase (CYP24A1, CYP27B1) in the kidney was performed.</p><p>[Results] P intake was proportional to the feeding concentration. Blood P concentration increased in the high-P diet group, but no change was observed in blood Ca concentration. The expression of slc34a2b in the jejunum and CYP24A1 in the kidney tended to increase in the high-P diet group. There were no differences between groups in the ileum. Kidney CYP27B1 was significantly increased in the high-P diet group compared to the low-P diet group.</p><p>[Discussion] Changes in transporters related to phosphorus absorption were confirmed in the jejunum, suggesting that phosphorus absorption in the intestine is mainly carried out in the jejunum. During early kidney injury, phosphorus homeostasis was regulated in the jejunum rather than the kidney. Furthermore, an increase in the expression level of CYP27B1 in the kidney was observed, suggesting an increase in the amount of calcitriol synthesis.</p>
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Pathophysiological analysis of repeated dose toxicity study of Ethyl Carbamate (EC;Urethane) in mice
OHASHI Sayaka, KAJIKAWA Akane, MAEKAWA Tatsuya, KEMURIYAMA Noriko, TOTSUKA Yukari, MIYAJIMA Katsuhiro
Annual Meeting of the Japanese Society of Toxicology 2024 The Japanese Society of Toxicology
Language：Japanese
<p>EC is one of the chemicals unintentionally produced during fermentation; it is classified by IARC as probably carcinogenic to humans. In this study, we evaluated the toxicological effects of EC in short-term administration on the major organs in mice, particularly the lungs and liver.</p><p>Six-week-old male C57BL/6J mice were treated with drinking water containing EC at doses of 300, 1000 and 2000 ppm for 4 weeks. The control group was fed tap water ad libitum. The diet was solid feed MF, and body weight and water consumption were measured. At the end of the treatment period, animals were dissected for pathological analysis.</p><p>The EC-treated group showed a decreasing trend in both body weight and water consumption compared to the control group. Serum AST and T-BIL were tended to increase.</p><p>Histopathologically, there were no obvious changes in the lungs and liver, but immunohistochemical staining showed an increase in F4/80-positive macrophages in both organs in the high-dose group. Gene expression analysis showed increased MCP-1 and IL-6 in the lungs and increased or a trend toward increased IL-1β, TNFα and MCP-1 in the liver.</p><p>No obvious impairment changes were observed in any of the organs in this study. However, in the liver and lungs, there was an increase in tissue macrophages and a trend toward increased inflammation-related genes, suggesting that EC may influence the induction of inflammation in these organs.</p>
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Impact on liver pathology via novel targets of SREBP-1
KEMURIYAMA Noriko, MANDOKORO Hina, LINFENG Gao, SATO Shiho, MIWA Taisei, MAEKAWA Tatsuya, NAKAE Dai, MIYAJIMA Katsuhiro
Annual Meeting of the Japanese Society of Toxicology 2024 The Japanese Society of Toxicology
Language：Japanese
<p>Aim: Sterol regulatory element-binding protein-1 (SREBP-1) is a transcription factor that regulates lipid synthesis, and its excessive activation is thought to promote obesity and abnormal lipid metabolism. This study aimed to clarify the possible involvement of SREBP-1 in metabolic regulation, as well as in inflammation and fibrosis-associated pathologies such as NASH. </p><p>Methods: Altered gene expression by the SREBP-1 knocking-down with siRNA was assessed in human hepatoma cell line HepG2 cells, using RNA-Seq. for the comprehensive exploration. In addition, SREBP-1a and SREBP-1c were overexpressed in human embryonic kidney cell line HEK293 cells for qRT-PCR and Luc assays. The association of IL-21 with ER stress and fibrosis was also assessed using HepG2 cells and the human hepatic stellate cell line LX-2. </p><p>Results: RNA-Seq. revealed the decrease of the IL-21R expression, which was confirmed by qRT-PCR. In addition, the IL-21R expression was significantly increased by the overexpression of SREBP-1a and SREBP-2 in HEK293 cells. Stimulation of ER stress and TGF-β1 in HepG2 and LX-2 induced SREBP-1a and IL-21R expression. Furthermore, simultaneous stimulation with IL-21 was suggested to further enhance ER stress and activate stellate cells, such as increased CHOP gene expression and collagen production. </p><p>Conclusion: We have previously reported that IL-21R KO mice exhibit suppressed liver fibrosis in NASH (JSOT2023). In the present study, we suggest that SREBP-1a may be involved in hepatic ER stress and fibrosis, apart from lipid metabolism, via the regulation of IL-21R expression.</p>
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Analysis of the relationship between blood levels of Mac-2 binding protein (Mac-2bp) and hepatic lesion in a mouse model of NASH
KAMINO Ryohei, UECHI Teppei, TOHMA Marika, KEMURIYAMA Noriko, SASASE Tomohiko, MAEKAWA Tatsuya, NAKAE Dai, MIYAJIMA Katsuhiro
Annual Meeting of the Japanese Society of Toxicology 2024 The Japanese Society of Toxicology
Language：Japanese
<p>Purpose: Mac-2 binding protein (Mac-2bp) is a secreted glycoprotein known to be a ligand for Galectin-3, which is thought to regulate cell adhesion through interaction with Galectin-3. The association between blood levels of Mac-2bp and chronic liver diseases, including NASH, has been reported. In this study, we analyzed the relationship between serum Mac-2bp levels and pathological changes in a diet-induced mouse model of NASH.</p><p>Materials and Methods: Six-week-old male C57BL/6 mice were fed ad libitum a basal diet and a choline-deficient methionine-reduced high-fat amino acid diet (CDAHFD). Feeding periods of 2, 8, and 52 weeks were established. At the end of each period, blood and liver samples were collected for the various analyses.</p><p>Results and discussion: Serum Mac-2bp levels increased from 2 weeks in the CDAHFD group, and then showed further increases. In the liver, significant hepatocellular fatty change from 2 weeks, inflammation and fibrosis from 8 weeks, and neoplastic lesions with nodular masses at 52 weeks in the CDAHFD group. Liver fibrosis imaging by Sirius red staining of liver tissue, the amount of hydroxyproline in the liver, and the expression of fibrosis-related genes increased in a feeding period-dependent manner. These changes were correlated with serum Mac-2bp levels. Furthermore, some associations were also observed in the liver tumor marker α-fetoprotein, the size of nodular lesions, and serum Mac-2bp levels. Based on these results, serum Mac-2bp may be a potential biomarker for liver tumor as well as liver fibrosis in a mouse model of NASH.</p>
Committee Memberships 【 display / non-display 】
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日本毒性学会 評議員
2023.06
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日本毒性学会認定トキシコロジスト
2011.10
Committee type：Academic society
Social Activities 【 display / non-display 】
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ネブラスカ州立大学の学生への講義
Role(s)： Lecturer
2024.05
Audience： College students
Type：Visiting lecture
食に関する毒性と、ゼブラフィッシュを用いた毒性試験について紹介