Phosphate metabolism neural network and disruption

• Project/Area Number: 17K09728
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: The University of Tokushima
• Principal Investigator: SEGAWA. Hiroko 徳島大学, 大学院医歯薬学研究部(医学域), 講師 (70325257)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: リン / 腎臓 / 腸 / 唾液線 / リン酸 / トランスポーター / 腸管 / 多臓器調節 / 唾液腺 / 神経

Outline of Final Research Achievements

In this study, we conducted the following studies to clarify the existing multi-organ network without regulatory factors. 1)Gastrointestinal tract -Salivary glands, 2) Gastrointestinal tract -Kidney, 3) Gastrointestinal tracts -Nerve.
The present study suggested that there is a nerve-mediated interaction in the Pi load through the intestinal tract. Intestinal-specific Pi transporter knockout mice were disrupted in the Pi-loading response, suggesting that the intestinal Pi transporter is one of the molecules that is sensitive to Pi level in the intestinal lumen.

Academic Significance and Societal Importance of the Research Achievements

生体内において、リン濃度は厳密に調節されているが、これまでリン代謝はカルシウム代謝に付随した調節系で制御されていると考えられて来た。近年新しいリン代謝調節系が明らかとなってきた。しかし、未だ不明な点が多い事、様々な分子が同定されたが、それらの調節機構を検討された臓器は限られている。本研究は、特に消化管に注目し、消化管と多臓器との新しい繋がりを導くことを目的として行なった。このメカニズムの解明は正常成長不全、CKD 患者、高齢者における治療につながると期待できる。また、唾液腺を分子標的とする新しいリン調節薬の開発が期待できる。

Research Products

• [Journal Article] Role of sodium-dependent Pi transporter/Npt2c on Pi homeostasis in klotho knockout mice different properties between juvenile and adult stages. (2020)
  • Author(s): Hanazaki A, Ikuta K, Sasaki S, Sasaki S, Koike M, Tanifuji K, Arima Y, Kaneko I, Shiozaki Y, Tatsumi S, Hasegawa T, Amizuka N, Miyamoto KI, Segawa H.
  • Journal Title: Physiol Rep. Volume: Feb;8(3) Issue: 3 Pages: 1-16
  • DOI: 10.14814/phy2.14324
  • Peer Reviewed / Open Access
• [Journal Article] Role of the putative PKC phosphorylation sites of the type IIc sodium-dependent phosphate transporter in parathyroid hormone regulation. (2019)
  • Author(s): Fujii Toru, Segawa Hiroko, Hanazaki Ai, Nishiguchi Shiori, Minoshima Sakura, Ohi Akiko, Tominaga Rieko, Sasaki Sumire, Tanifuji Kazuya, Koike Megumi, Arima Yuki, Shiozaki Yuji, Kaneko Ichiro, Ito Mikiko, Tatsumi Sawako, Miyamoto Ken-ichi
  • Journal Title: Clin Exp Nephrol Volume: 23 Pages: 898-907
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of opossum kidney NaPi-IIc sodium-dependent phosphate transporter to understand Pi handling in human kidney. (2019)
  • Author(s): Fujii T, Shiozaki Y, Segawa H, Nishiguchi S, Hanazaki A, Noguchi M, Kirino R, Sasaki S, Tanifuji K, Koike M, Yokoyama M, Arima Y, Kaneko I, Tatsumi S, Ito M, Miyamoto KI.
  • Journal Title: Clin Exp Nephrol Volume: 23(3) Issue: 3 Pages: 313-324
  • DOI: 10.1007/s10157-018-1653-4
  • Peer Reviewed / Open Access
• [Journal Article] Systemic network for dietary inorganic phosphate adaptation among three organs. (2019)
  • Author(s): Ikuta K, Segawa H, Hanazaki A, Fujii T, Kaneko I, Shiozaki Y, Tatsumi S, Ishikawa Y, Miyamoto KI
  • Journal Title: Pflugers Archiv - European Journal of Physiology Volume: 471(1） Issue: 1 Pages: 123-136
  • DOI: 10.1007/s00424-018-2242-9
  • Peer Reviewed / Open Access
• [Journal Article] The Role of Extracellular Phosphate Levels on Kidney Disease Progression in a Podocyte Injury Mouse Model (2019)
  • Author(s): Maeda Akira、Fukushima Naoshi、Horiba Naoshi、Segawa Hiroko、Miyamoto Ken-ichi
  • Journal Title: Nephron Volume: 1 Issue: 2 Pages: 1-12
  • DOI: 10.1159/000497118
  • Peer Reviewed
• [Journal Article] Eldecalcitol Causes FGF23 Resistance for Pi Reabsorption and Improves Rachitic Bone Phenotypes in the Male Hyp Mouse. (2018)
  • Author(s): Kaneko I, Segawa H, Ikuta K, Hanazaki A, Fujii T, Tatsumi S, Kido S, Hasegawa T, Amizuka N, Saito H, Miyamoto KI.
  • Journal Title: Endocrinology Volume: 159(7) Issue: 7 Pages: 2741-2758
  • DOI: 10.1210/en.2018-00109
  • Peer Reviewed / Open Access
• [Journal Article] A Role of Intestinal Alkaline Phosphatase 3 (Akp3) in Inorganic Phosphate Homeostasis (2018)
  • Author(s): Sasaki Shohei、Segawa Hiroko、Hanazaki Ai、Kirino Ruri、Fujii Toru、Ikuta Kayo、Noguchi Miwa、Sasaki Sumire、Koike Megumi、Tanifuji Kazuya、Shiozaki Yuji、Kaneko Ichiro、Tatsumi Sawako、Shimohata Takaaki、Kawai Yoshichika、Narisawa Sonoko、Millan Jose Luis、Miyamoto Ken-ichi
  • Journal Title: Kidney and Blood Pressure Research Volume: 43 Issue: 5 Pages: 1409-1424
  • DOI: 10.1159/000493379
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] NAD metabolism and the SLC34 family: evidence for a liver-kidney axis regulating inorganic phosphate (2018)
  • Author(s): Tatsumi Sawako、Katai Kanako、Kaneko Ichiro、Segawa Hiroko、Miyamoto Ken-ichi
  • Journal Title: Pflugers Archiv - European Journal of Physiology Volume: 471 Issue: 1 Pages: 109-122
  • DOI: 10.1007/s00424-018-2204-2
  • Peer Reviewed
• [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] 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] 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
• [Presentation] Intestinal Alkaline Phosphatase（IAP）による内環境制御と腎保護作.The role of Intestinal Alkaline Phosphatase(IAP)for Intestinal environmental control and renal protection (2019)
  • Author(s): 桐野留里、瀬川博子、花崎愛、佐々木すみれ、小池萌、谷藤和也、金子一郎、宮本賢一
  • Organizer: 第3回日本Uremic Toxin研究会学術集会
• [Presentation] 高リン血症におけるリン管理：Nampt/NAD代謝の検討 (2019)
  • Author(s): 中辻翔也、桑原煩治、室岡響、田口裕子、古川菜摘、森由貴、古澤みなみ、瀬川博子、 宮本賢一、辰巳佐和子
  • Organizer: 第7回日本腎栄養代謝研究回学術集会・総会
• [Presentation] ビタミンDとうつ病の関係：セロトニン代謝の解析 (2019)
  • Author(s): 金子一郎、Mark R Haussier、Peter W Jurutka、瀬川博子、宮本賢一
  • Organizer: 第7回日本腎栄養代謝研究回学術集会・総会
• [Presentation] 腸管ニコチンアミドホスホリボシルトランスフェラーゼのリン吸収抑制効果の検討 (2019)
  • Author(s): 辰巳佐和子、中辻翔也、河田美紀、桑原煩治、金子一郎、瀬川博子、宮本賢一
  • Organizer: 第66回日本栄養改善学会学術総会
• [Presentation] ビタミンDによる小腸リン輸送調節機序の解明 (2019)
  • Author(s): 金子一郎、瀬川博子、加藤茂明、宮本賢一
  • Organizer: 第66回日本栄養改善学会学術総会
• [Presentation] Intestinal Alkaline Phosphatase(IAP)による腸内環境制御と腎保護作用 (2019)
  • Author(s): 瀬川博子、有馬佑貴、小池萌、谷藤和也、佐々木すみれ、花崎愛、金子一郎、宮本賢一
  • Organizer: 第66回日本栄養改善学会学術総会
• [Presentation] リン代謝ネットワーク調節機構と疾患 (2019)
  • Author(s): 瀬川博子
  • Organizer: 第61回歯科基礎医学会学術大会
  • Invited
• [Presentation] Intestinal Alkaline Phosphatase(IAP)による腸管リン代謝制御と腎保護作用 (2019)
  • Author(s): 有馬佑貴、瀬川博子、花崎愛、佐々木すみれ、小池萌、谷藤和也、野沢愛、金子一郎、宮本賢一
  • Organizer: 第52回日本栄養・食糧学会 中国・四国支部大会
• [Presentation] PiT-2 Is the Main Transporter Responsible for Intestinal Phosphate Absorption in Human. (2019)
  • Author(s): Ichida I, Weis D, Ohtomo S, Kaesler N, Kuppe C, Yamamoto T, Murao N, Segawa H, Kawabe Y, Horiba N, Miyamoto K, Floege J.
  • Organizer: American Society of Nephrology kidney week 2019
  • Int'l Joint Research
• [Presentation] Intestinal Environmental Control and Renal Protection by Intestinal Alkaline Phosphatase (IAP) (2019)
  • Author(s): Segawa H, Sasaki S, Arima Y, Hanazaki A, Koike M, Tanifuji K, Miyamoto KI.
  • Organizer: American Society of Nephrology kidney week 2019
  • Int'l Joint Research
• [Presentation] Possible Clinical Relevance of Growth Hormone-Stimulated α-Klotho Upregulation. (2019)
  • Author(s): Sato T, Koike M, Segawa H, Miyamoto KI, Fukagawa M.
  • Organizer: American Society of Nephrology kidney week 2019
  • Int'l Joint Research
• [Presentation] Phosphate balance in the body and epithelial phosphate transporters. (2019)
  • Author(s): Segawa H, Shiozaki Y, Kaneko I, Miyamoto K.
  • Organizer: 9th Federation of the Asian and Oceanian Physiological Societies (FAOPS) CONGRESS
  • Int'l Joint Research / Invited
• [Presentation] Systemic network for phosphate homeostasis in the body (2019)
  • Author(s): Segawa H, Kaneko I, Miyamoto K.
  • Organizer: The 7th International Conference on Food Factors (ICoFF2019) / The 12thInternational Conference and Exhibition on Nutraceuticals and Functional Foods 2019 (ISNFF2019)
  • Int'l Joint Research / Invited
• [Presentation] FGF23-リンによる腸管窒素吸収調節 (2018)
  • Author(s): 瀬川博子、古谷順也、金子一郎、宮本賢一
  • Organizer: 第2回日本UremicToxin 研究学術集会. 東京国際フォーラム
• [Presentation] Dietary Phosphate intake Patterns in HD Patients (2018)
  • Author(s): Hiroko Segawa
  • Organizer: KDIGO CKD-MBD Implementation Summit, 京王プラザホテル（東京）4/27-29(28).
  • Int'l Joint Research / Invited
• [Presentation] ビタミンDが制御する腸管リン吸収機序の解明 (2018)
  • Author(s): 金子一郎、瀬川博子、野津圭二郎、生田かよ、藤井公、花崎愛、張哲然、加藤茂明、宮本賢一
  • Organizer: 第72回日本栄養・食糧学会大会. 岡山コンベンションセンター/岡山県立大学（岡山市）2018/5/11-13（13）
• [Presentation] 分子腎臓栄養学－基礎研究の理解－ (2018)
  • Author(s): 瀬川博子
  • Organizer: 第6回日本腎栄養代謝研究会学術集会・総会. 千里ライフサイエンスセンター（豊中市）2018/7/14-15.
  • Invited
• [Presentation] リン代謝－多臓器連関制御－ (2018)
  • Author(s): 瀬川博子
  • Organizer: 第36回日本骨代謝学会学術集会. 長崎ブリックホール（長崎市）. 2018/7/26-28（27）
  • Invited
• [Presentation] Daily oscillation of the plasma inorganic phosphate concentration; Impact of Nampt deficient mice (2018)
  • Author(s): Sawako Tatsumi, Ichiro Kaneko, Hiroko Segawa, Ken-ichi Miyamoto
  • Organizer: ASN (American Society of Nephrology), Kidney Week 2018. San Diego, CA. October 25, 2018
• [Presentation] 食物無機リン酸適応唾液－腸管－腎臓ネットワーク (2018)
  • Author(s): 谷藤和也、瀬川博子、生田かよ、花崎愛、佐々木すみれ、小池萌、金子一郎、石川康子、宮本賢一
  • Organizer: 第51回日本栄養・食糧学会中国・四国支部大会広島大学（東広島キャンパス）生物生産学部（東広島市）2018/11/17-18（18）
• [Presentation] Gastrointestinal phosphate handling (2018)
  • Author(s): Hiroko Segawa
  • Organizer: ISN FRONTIERS MEETINGS
  • Int'l Joint Research / Invited
• [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] 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
  • Int'l Joint Research
• [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
• [Book] 消化管からみた健康・栄養. 第3章 タンパク質・アミノ酸、糖、リンの吸収, .51-69. (2018)
  • Author(s): 瀬川博子
  • Total Pages: 259
  • Publisher: 建帛社.