Clarification of multi-organ communication controlling with phosphate and vitamin D metabolism.

• Project/Area Number: 15K19455
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: The University of Tokushima
• Principal Investigator: KANEKO Ichiro 徳島大学, 大学院医歯薬学研究部(医学系), 助教 (40389515)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: リン / ビタミンD / 慢性腎臓病 / VDR

Outline of Final Research Achievements

Bone-mineral metabolic abnormalities associated with Chronic Kidney Disease (CKD) are "multiple organ diseases" caused by failure of phosphate metabolism. In this study, we analyzed the mechanism of abnormal mineral metabolism across multiple organs and its therapeutic effects. In CKD-induced vitamin D receptor (VDR)-deficient mice, suppression of blood urea nitrogen and phosphorus elevation was observed, suggesting that the inhibition of VDR is effective for renal protection. Furthermore, the importance of tissue selective VDR action and the therapeutic effects by low phosphate diet or vitamin D administration are evaluated.
Also, we comprehensively detected metabolic (biological) products using metabolome analyzers, and obtained enormous data. Based on these results, we are attempting to identify early diagnostic markers for CKD-Mineral Bone Disorder and predictive markers for multiple organ complications.

Research Products

• [Journal Article] Effect of Npt2b deletion on intestinal and renal inorganic phosphate (Pi) handling (2018)
  • Author(s): Ikuta K, Segawa H, Sasaki S, Hanazaki A, Fujii T, Kushi A, Kawabata Y, Kirino R, Sasaki S, Noguchi M, Kaneko I, Tatsumi S, Ueda O, Wada NA, Tateishi H, Kakefuda M, Kawase Y, Ohtomo S, Ichida Y, Maeda A, Jishage KI, Horiba N, Miyamoto KI.
  • Journal Title: Clin Exp Nephrol. Volume: 印刷中 Issue: 3 Pages: 1497-1503
  • DOI: 10.1007/s10157-017-1497-3
  • Peer Reviewed
• [Journal Article] The sodium phosphate cotransporter family and nicotinamide phosphoribosyltransferase contribute to the daily oscillation of the plasma inorganic phosphate concentration. (2018)
  • Author(s): Miyagawa A, Tatsumi S, Takahama W, Fujii O, Nagamoto K, Kinoshita E, Nomura K, Ikuta K, Fujii T, Hanazaki A, Kaneko I, Segawa H, Miyamoto KI.
  • Journal Title: Kidney Int. Volume: 印刷中 Issue: 5 Pages: 1073-1085
  • DOI: 10.1016/j.kint.2017.11.022
  • Peer Reviewed
• [Journal Article] Gene Expression Profiling and Assessment of Vitamin D and Serotonin Pathway Variations in Patients With Irritable Bowel Syndrome. (2018)
  • Author(s): Dussik CM, Hockley M, Grozi A, Kaneko I, Zhang L, Sabir MS, Park J, Wang J, Nickerson CA, Yale SH, Rall CJ, Foxx-Orenstein AE, Borror CM, Sandrin TR, Jurutka PW.
  • Journal Title: J Neurogastroenterol Motil. Volume: 24 Issue: 1 Pages: 96-106
  • DOI: 10.5056/jnm17021
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effect of Osteocyte-Ablation on Inorganic Phosphate Metabolism: Analysis of Bone-Kidney-Gut Axis (2017)
  • Author(s): Fujii O, Tatsumi S, Ogata M, Arakaki T, Sakaguchi H, Nomura K, Miyagawa A, Ikuta K, Hanazaki A, Kaneko I, Segawa H, Miyamoto KI.
  • Journal Title: Front Endocrinol (Lausanne) Volume: 8
  • DOI: 10.3389/fendo.2017.00359
  • NAID: 120006550813
  • Peer Reviewed / Open Access
• [Journal Article] Update on recent progress in vitamin D research. Vitamin D and muscle tissues. (2017)
  • Author(s): Kaneko I, Miyamoto KI, Nikawa T.
  • Journal Title: Clin Calcium. Volume: 27 Pages: 1571-1578
  • Peer Reviewed
• [Journal Article] 活性型ビタミンDは、トリプトファン水酸化酵素およびレプチン遺伝子発現を制御する。 (2017)
  • Author(s): Kaneko I, Sabir MS, Dussik CM, Whitfield GK, Karrys A, Hsieh JC, Haussler MR, Meyer MB, Pike JW, Jurutka PW.
  • Journal Title: ビタミン Volume: 91 Pages: 132-134
  • NAID: 130006694397
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Regulation of renal phosphate handling:inter-organ communication in health and disease. (2016)
  • Author(s): Tatsumi S, Miyagawa A, Kaneko I, Shiozaki Y, Segawa H, Miyamoto K.
  • Journal Title: J Bone Miner Metab. Volume: 34(1) Issue: 1 Pages: 1-10
  • DOI: 10.1007/s00774-015-0705-z
  • Peer Reviewed / Open Access
• [Journal Article] Control of phosphate balance by the kidney and intestine. (2016)
  • Author(s): Kaneko I, Tatsumi S, Segawa H,Miyamoto KI.
  • Journal Title: Clin Exp Nephrol. Volume: Mar;21 Issue: S1 Pages: 21-26
  • DOI: 10.1007/s10157-016-1359-4
  • Peer Reviewed / Open Access
• [Journal Article] 尿細管リン再吸収障害によるくる病／骨軟化症. (2016)
  • Author(s): 金子一郎, 瀬川博子, 辰巳佐和子, 宮本賢一.
  • Journal Title: 腎と透析診療方針2016, 腎と透析vol80増刊号 Volume: 80 Pages: 300-306
  • Peer Reviewed
• [Journal Article] 遺伝性リン代謝異常 (2015)
  • Author(s): 金子一郎、瀬川博子、辰巳佐和子、宮本賢一
  • Journal Title: 日本腎臓学会誌 Volume: 57 Pages: 758-765
  • Peer Reviewed
• [Journal Article] FGF23 gene regulation by 1,25-dihydroxyvitamin D: opposing effects in adipocytes and osteocytes. (2015)
  • Author(s): Kaneko I, Saini RK, Griffin KP, Whitfield GK, Haussler MR, Jurutka PW.
  • Journal Title: J Endocrinol. Volume: 226 Issue: 3 Pages: 155-166
  • DOI: 10.1530/joe-15-0225
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Relationship between sodium-dependent phosphate transporter (NaPi-IIc) function and cellular vacuole formation in opossum kidney cells (2015)
  • Author(s): Shiozaki Y, Segawa H, Ohnishi S, Ohi A, Ito N, Kaneko I, Kido S, Tatsumi S, Miyamoto K.
  • Journal Title: The Journal of Medical Investigation Volume: 62 Issue: 3.4 Pages: 209-218
  • DOI: 10.2152/jmi.62.209
  • NAID: 130005099143
  • ISSN: 1343-1420, 1349-6867
  • Peer Reviewed / Open Access
• [Presentation] 腎臓と他の臓器相関による生体内リン代謝調節機構 (2018)
  • Author(s): 瀬川 博子、金子 一郎、宮本 賢一.
  • Organizer: 第95回日本生理学会大会
  • Invited
• [Presentation] 骨－腎臓連関を介した食餌性リン感受機 (2017)
  • Author(s): 辰巳佐和子、緒方雅央、新垣友啓、藤井理、金子一郎、瀬川博子、宮本賢一.
  • Organizer: 第71回日本栄養食糧学会大会
• [Presentation] 生体内リン恒常性における Intestinal Alkaline Phosphatase (IAP) の役割 (2017)
  • Author(s): 瀬川博子、佐々木祥平、結城志帆子、金子一郎、辰巳佐和子、宮本賢一.
  • Organizer: 第71回日本栄養食糧学会大会
• [Presentation] 生体内リン恒常性におけるアルカフォスファターゼの役割. (2017)
  • Author(s): 桐野留里、瀬川博子、金子一郎、辰巳佐和子、宮本賢一.
  • Organizer: 第4回日本栄養改善学会四国支部学術総会
• [Presentation] 水溶性ビタミンB3と腸管上皮機能. (2017)
  • Author(s): 藤井理、辰巳佐和子、金子一郎、瀬川博子、宮本賢一.
  • Organizer: 第64回日本栄養改善学会学術総会
• [Presentation] 脳機能における活性型ビタミンDの役割. (2017)
  • Author(s): 金子一郎、瀬川博子、辰巳佐和子、宮本賢一.
  • Organizer: 第64回日本栄養改善学会学術総会
• [Presentation] 生体内リン恒常性における腸管アルカリフォスファターゼの役割 (2017)
  • Author(s): 桐野留里、瀬川博子、佐々木すみれ、金子一郎、辰巳佐和子、宮本賢一.
  • Organizer: 第64回日本栄養改善学会学術総会
• [Presentation] 形態の異なるリン化合物接種に対する生体への影響 (2017)
  • Author(s): 佐々木すみれ、瀬川博子、桐野留里、金子一郎、辰巳佐和子、宮本賢一.
  • Organizer: 第64回日本栄養改善学会学術総会
• [Presentation] In Vivo Responses of Phosphorus-Based Food Additives with Different Forms. (2017)
  • Author(s): Fujii T, Kawabata Y, Segawa H, Hanazaki A, Ikuta K, Kushi A, Kaneko I, Tatsumi S, Miyamoto K.
  • Organizer: American Society of Nephrology, Kidney week.
  • Int'l Joint Research
• [Presentation] 腸管NAD+合成律速酵素（Nampt）と全身性NAD+代謝 (2017)
  • Author(s): 木下瑛美、辰巳佐和子、藤井理、張哲然、金子一郎、瀬川博子、宮本賢一.
  • Organizer: 第50回日本栄養食糧学会 中国四国支部大会
• [Presentation] リン利尿因子FGF23の転写調節機序の解明 (2017)
  • Author(s): 金子一郎、Saini RK, Whitfield GK、伊藤美紀子、瀬川博子、辰巳佐和子、宮本賢一、Haussler MR、Jurutka PW.
  • Organizer: 第50回日本栄養食糧学会 中国四国支部大会
• [Presentation] 栄養素輸送担体と健康・疾患「腸管リン吸収と慢性腎臓病」 (2017)
  • Author(s): 瀬川 博子、金子 一郎、辰巳 佐和子、宮本 賢一.
  • Organizer: 第71回日本栄養食糧学会大会
  • Invited
• [Presentation] Salivary Pi Handling May Be under the Control of Gastrointestinal Pi Sensing. (2016)
  • Author(s): Kayo Ikuta, Hiroko Segawa, Shihoko Yuki, Ichiro Kaneko, Ai Hanazaki, Toru Fujii, Aoi Kushi, Sawako Tatsumi, Ken-ichi Miyamoto.
  • Organizer: American Society of Nephrology. Kidney Week 2016.
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2016-11-15
  • Int'l Joint Research
• [Presentation] Hepatectomy-Induced Hypophosphatemia: Mechanisms Underlying Downregulation of Phophate Transport in the Small Intestine. (2016)
  • Author(s): Sawako Tatsumi, Atsumi Miyagawa, Osamu Fujii, Mao Ogata, Ichiro Kaneko, Hiroko Segawa, Keni-ichi Miyamoto.
  • Organizer: American Society of Nephrology. Kidney Week 2016.
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2016-11-15
  • Int'l Joint Research
• [Presentation] リン代謝動態の概日リズム形成機序解明. (2016)
  • Author(s): 高濱和子, 辰巳佐和子, 宮川淳美， 藤井理, 新垣友啓, 緒方雅央, 木下瑛美, 金子一郎, 瀬川博子, 宮本賢一.
  • Organizer: 第49回日本栄養・食糧学会 中国・四国支部大会
  • Place of Presentation: 徳島大学（徳島県徳島市）
  • Year and Date: 2016-11-12
• [Presentation] 脳機能におけるビタミンDの役割 (2016)
  • Author(s): 金子一郎、Jui-Cheng Hsieh、G. Kerr Whitfield、辰巳佐和子、瀬川博子、宮本賢一、Mark R. Haussler、Peter W. Jurutka.
  • Organizer: 第68回日本ビタミン学会
  • Place of Presentation: 富山国際会議場（富山県富山市）
  • Year and Date: 2016-06-17
• [Presentation] 形態の異なるリン化合物接種に対する生体への影響. (2016)
  • Author(s): 川端優佳, 瀬川博子, 結城志帆子, 中山彰吾, 藤井公, 生田かよ, 花崎愛, 野津圭二郎, 西口詩織, 金子一郎, 辰巳佐和子, 宮本賢一.
  • Organizer: 第70回日本栄養・食糧学会大会
  • Place of Presentation: 神戸ポートピアアホテル（兵庫県神戸市）、武庫川女子大学（兵庫県西宮市）
  • Year and Date: 2016-05-13
• [Presentation] FGF23: A Nurr1-dependent phosphaturic hormonegene that is transcriptionally regulated by 1.25-dihydroxyvitamin D. (2016)
  • Author(s): Ichiro Kaneko, Rimpi K. Saini, G. Kerr Whitfield, Mikiko Ito, Hiroko Segawa, Sawako Tatsumi, Ken-ichi Miyamoto, Mark R. Haussler, and Peter W. Jurutka.
  • Organizer: XVIII International Congress on Nutrition and Metabolism in Renal Desease (ICRNM2016)
  • Place of Presentation: Okinawa Convention Center (沖縄県宜野湾市)
  • Year and Date: 2016-04-19
  • Int'l Joint Research
• [Presentation] Genetic Deletion of NaPi-2c Rescue Phenotype of Klotho Knockout Mice without Improving Severe Hyperphosphatemia. (2015)
  • Author(s): Hanasaki A, Segawa H, Ikuta K, Fujii T, Kaneko I, Yuki S, Nishiguchi S, Notsu K, Shiozaki Y, Tatsumi S, Miyamoto KI.
  • Organizer: American Society of Nephrology, Kidney Week 2015
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2015-11-03
  • Int'l Joint Research
• [Presentation] The role of Na+-dependent Phosphate transporters in the body. (2015)
  • Author(s): Segawa H, Kaneko I, Shiozaki Y, Tatsumi S, Miyamoto KI.
  • Organizer: Asian Congress of Nutrition 2015
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-05-14
  • Int'l Joint Research / Invited
• [Book] NEXT分子栄養学 (2018)
  • Author(s): 池田彩子、井上裕康、沖嶋直子、香川靖雄、金子一郎、亀井康富、木戸慎介、桑波田雅士、竹中優、立花宏文、中田理恵子、服部正平、松本高広、三坂巧、宮本賢一、山下広美、山田一哉、山本浩範
  • Total Pages: 223
  • Publisher: 講談社
  • ISBN: 9784061553972
• [Book] Molecular Basis of Nutrition and Aging (2016)
  • Author(s): Mark R. Haussler, Rimpi K. Saini, Marya S. Sabir, Christopher M. Dussik, Zainab Khan, G. Kerr Whitfield, Kristin P. Griffin, Ichiro Kaneko and Peter W. Jurutka.
  • Total Pages: 784
  • Publisher: Academic Press, 2016
• [Book] Molecular, Genetic, and Nutritional Aspects of Major and Trace Minerals (2016)
  • Author(s): Ichiro Kaneko, Hironori Yamamoto, Kayo Ikuta, Sawako Tatsumi, Hiroko Segawa, Ken-ichi Miyamoto.
  • Total Pages: 558
  • Publisher: ELSEVIER
• [Book] 高リン血症治療BestChoiceエキスパートのコツから学ぶ (2016)
  • Author(s): 宮川淳美, 金子一郎, 宮本賢一.
  • Total Pages: 156
  • Publisher: 医薬ジャーナル