Evolution of neo-mineral knowledge understanding CKD-MBD

2013 Fiscal Year Final Research Report

• Project/Area Number: 23689045
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Kidney internal medicine
• Research Institution: The University of Tokushima
• Principal Investigator: SEGAWA Hiroko 徳島大学, ヘルスバイオサイエンス研究部, 講師 (70325257)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: リン利尿 / 腎臓 / 小腸 / 唾液腺 / トランスポーターランスポーター / CKD / MBD

Research Abstract

Hyperphosphatemia is contributes to vascular calcification in patients with chronic kidney disease and hemodialysis patients and is associated with cardiac mortality. Recently, several studies reported the relationship among salivary phosphate concentration, renal function, serum phosphate concentration, and the potential target of new therapy for hypephosphatemia. However, it is unclear the inorganic phosphate (Pi) handling mechanisms in salivary glands. In the present study, we investigated the Pi handling in salivary glands. In wild-type mice fed a high Pi diet, the levels of plasma and salivary Pi are significantly higher than those in mice fed a low Pi diet. In Npt2b+/- mice, the salivary Pi concentrations were significantly increased compared with those in Npt2b+/+ mice. The present study suggests that salivary Pi levels correlate with dietary Pi content, and salivary glands paly a role for phosphate homeostasis system in the body.

Research Products

• [Journal Article] Downregulation of renal type IIa sodium-dependent phosphate cotransporter during lipopolysaccharide-induced acute inflammation (2014)
  • Author(s): Ikeda S, Yamamoto H, Masuda M, Takei Y, Nakahashi O, Kozai M, Tanaka S, Nakao M, Taketani Y, Segawa H, Iwano M, Miyamoto K, Takeda E
  • Journal Title: Am J Physiol Renal Physiol Volume: 306 Pages: F744-750
  • DOI: 10.1152/ajprenal.00474.2013
  • Peer Reviewed
• [Journal Article] Role of serine 249 of ezrin in the regulation of sodium-dependent phosphate transporter NaPi-IIa activity in renal proximal tubular cells (2013)
  • Author(s): Yamada F, Horie D, Nakamura A, Tanimura A, Yamamoto H, Segawa H, Ito M, Miyamoto K, Taketani Y, Takeda E
  • Journal Title: J Med Invest Volume: 60 Pages: 27-34
  • Peer Reviewed
• [Journal Article] Critical role of parathyroid hormone (PTH) receptor-1 phosphorylation in regulating acute responses to PTH (2013)
  • Author(s): Maeda A, Okazaki M, Baron DM, Dean T, Khatri A, Mahon M, Segawa H, Abou-Samra AB, Juppner H, Bloch KD, Potts JT, Jr., Gardella TJ
  • Journal Title: Proc Natl Acad Sci U S A Volume: 110 Pages: 5864-5869
  • DOI: 10.1073/pnas.1301674110
  • Peer Reviewed
• [Journal Article] Ezrin, a membrane cytoskeletal cross-linker, is essential for the regulation of phosphate and calcium homeostasis (2013)
  • Author(s): Hatano R, Fujii E, Segawa H, Mukaisho K, Matsubara M, Miyamoto K, Hattori T, Sugihara H, Asano S
  • Journal Title: Kidney Int Volume: 83 Pages: 41-49
  • DOI: 10.1038/ki.2012.308
  • Peer Reviewed
• [Journal Article] Activation of a non-cAMP/PKA signaling pathway downstream of the PTH/PTHrP receptor is essential for a sustained hypophosphatemic response to PTH infusion in male mice (2013)
  • Author(s): Guo J, Song L, Liu M, Segawa H, Miyamoto K, Bringhurst FR, Kronenberg HM, Juppner H
  • Journal Title: Endocrinology Volume: 154 Pages: 1680-1689
  • DOI: 10.1210/en.2012-2240
  • Peer Reviewed
• [Journal Article] Dietary inorganic phosphorus regulates the intestinal peptide transporter PepT1 (2013)
  • Author(s): Furutani J, Segawa H, Aranami F, Kuwahara S, Sugano M, Bannai K, Yamato H, Ito M, Miyamoto K
  • Journal Title: J Ren Nutr Volume: 23 Pages: e11-20
  • DOI: 10.1053/j.jrn.2012.02.006
  • Peer Reviewed
• [Journal Article] Fanconi-Bickel syndrome and autosomal recessive proximal tubulopathy with hypercalciuria (ARPTH) are allelic variants caused by GLUT2 mutations (2012)
  • Author(s): Mannstadt M, Magen D, Segawa H, Stanley T, Sharma A, Sasaki S, Bergwitz C, Mounien L, Boepple P, Thorens B, Zelikovic I, Juppner H
  • Journal Title: J Clin Endocrinol Metab Volume: 97 Pages: E1978-E1986
  • DOI: 10.1210/jc.2012-1279
  • Peer Reviewed
• [Journal Article] Identification and functional analysis of a splice variant of mouse sodium-dependent phosphate transporter Npt2c (2012)
  • Author(s): Kuwahara S, Aranami F, Segawa H, Onitsuka A, Honda N, Tominaga R, Hanabusa E, Kaneko I, Yamanaka S, Sasaki S, Ohi A, Nomura K, Tatsumi S, Kido S, Ito M, Miyamoto K
  • Journal Title: J Med Invest Volume: 59 Pages: 116-126
  • Peer Reviewed
• [Journal Article] Processing and stability of type IIc sodium-dependent phosphate cotransporter mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria (2012)
  • Author(s): Haito-Sugino S, Ito M, Ohi A, Shiozaki Y, Kangawa N, Nishiyama T, Aranami F, Sasaki S, Mori A, Kido S, Tatsumi S, Segawa H, Miyamoto K
  • Journal Title: Am J Physiol Cell Physiol Volume: 302 Pages: C1316-C1330
  • DOI: 10.1152/ajpcell.00314.2011
  • Peer Reviewed
• [Journal Article] Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b(+)/(-) mice (2011)
  • Author(s): Ohi A, Hanabusa E, Ueda O, Segawa H, Horiba N, Kaneko I, Kuwahara S, Mukai T, Sasaki S, Tominaga R, Furutani J, Aranami F, Ohtomo S, Oikawa Y, Kawase Y, Wada NA, Tachibe T, Kakefuda M, Tateishi H, Matsumoto K, Tatsumi S, Kido S, Fukushima N, Jishage K, Miyamoto K
  • Journal Title: Am J Physiol Renal Physiol Volume: 301 Pages: F1105-F1113
  • DOI: 10.1152/ajprenal.00663.2010
  • Peer Reviewed
• [Journal Article] Sodium-dependent phosphate cotransporters : lessons from gene knockout and mutation studies (2011)
  • Author(s): Miyamoto K, Haito-Sugino S, Kuwahara S, Ohi A, Nomura K, Ito M, Kuwahata M, Kido S, Tatsumi S, Kaneko I, Segawa H
  • Journal Title: J Pharm Sci Volume: 100 Pages: 3719-3730
  • DOI: 10.1002/jps.22614
  • Peer Reviewed
• [Journal Article] Transgenic overexpression of the extra-large Gsalpha variant XLalphas enhances Gsalpha-mediated responses in the mouse renal proximal tubule in vivo (2011)
  • Author(s): Liu Z, Segawa H, Aydin C, Reyes M, Erben RG, Weinstein LS, Chen M, Marshansky V, Frohlich LF, Bastepe M
  • Journal Title: Endocrinology Volume: 152 Pages: 1222-1233
  • DOI: 10.1210/en.2010-1034
  • Peer Reviewed
• [Journal Article] Hypophosphatemia in vitamin D receptor null mice : effect of rescue diet on the developmental changes in renal Na+ -dependent phosphate cotransporters (2011)
  • Author(s): Kaneko I, Segawa H, Furutani J, Kuwahara S, Aranami F, Hanabusa E, Tominaga R, Giral H, Caldas Y, Levi M, Kato S, Miyamoto K
  • Journal Title: Pflugers Arch Volume: 461 Pages: 77-90
  • DOI: 10.1007/s00424-010-0888-z
  • Peer Reviewed
• [Journal Article] Acute down-regulation of sodium-dependent phosphate transporter NPT2a involves predominantly the cAMP/PKA pathway as revealed by signaling-selective parathyroid hormone analogs
  • Author(s): Nagai S, Okazaki M, Segawa H, Bergwitz C, Dean T, Potts JT, Jr., Mahon MJ, Gardella TJ, Juppner H
  • Journal Title: J Biol Chem Volume: 86 2011 Pages: 1618-1626
  • DOI: 10.1074/jbc.M110.198416
  • Peer Reviewed
• [Presentation] Hepatectomy Hypophosphatemia : A Novel Phosphaturic Factor in the Liver Kidney Axis (2013)
  • Author(s): Nomura K, Tatsumi S, Miyagawa A, Shiozaki Y, Sasaki S, Segawa H, Miyamoto K
  • Organizer: American Society of Nephrology Annual Meeting
  • Place of Presentation: Georgia World Congress Center, Atlanta, GA, USA
  • Year and Date: 2013-11-08
• [Presentation] Molecular mechanisms of cadmium (Cd) dependent fibroblast growth factor 23 secretion in bone (2012)
  • Author(s): Kido S, Fujiwara M, Nomura K, Sasaki S, Shiozaki Y, Segawa H, Tatsumi S, Miyamoto K
  • Organizer: American Society of Nephrology Annual Meeting
  • Place of Presentation: San Diego Convention Center, San Diego, CA, USA.
  • Year and Date: 2012-11-02
• [Presentation] Mechanisms of hyperphosphatemia in the osteocyte-abelated mice (2012)
  • Author(s): Tatsumi S, Kamatani T, Nomura K, Yoshimi A, Shiozaki Y, Sasaki S, Manabe M, Kido S, Segawa H, Miyamoto K
  • Organizer: American Society of Nephrology Annual Meeting
  • Place of Presentation: San Diego Convention Center, CA, USA.
  • Year and Date: 2012-11-02
• [Presentation] The Membrane Cytoskeletal Crosslinker Ezrin Is Essential for the Regulation of Phosphate Homeostasis in the Kidney (2012)
  • Author(s): Hatano R, Segawa H, Tamura A, Miyamoto K, Tsukita S, Asano S
  • Organizer: American Society of Nephrology Annual Meeting
  • Place of Presentation: San Diego Convention Center, San Diego, CA, USA.
  • Year and Date: 2012-11-01
• [Presentation] Clinical consequences of gene mutations involved in renal phosphate transport (2012)
  • Author(s): Miyamoto K, Ohnishi S, Shiozaki Y, Segawa H, Tatsumi S
  • Organizer: International Symposium on Epithelial Barrier and Transport
  • Place of Presentation: Ritsumeikan University. Kusatsu, Shiga, Japan.
  • Year and Date: 2012-09-16
• [Presentation] CKDにおけるリン代謝異常:吸収と排泄における問題点 (2012)
  • Author(s): 瀬川博子、宮本賢一
  • Organizer: 第30回日本骨代謝学会学術集会
  • Place of Presentation: 京王プラザホテル、東京都
  • Year and Date: 2012-07-19
• [Presentation] Dietary inorganic phosphorus and intestinal peptide absorption (2012)
  • Author(s): Segawa H, Furutani J, Miyamoto K
  • Organizer: XVI International Congress on Nutrition and Metabolism in Renal Disease
  • Place of Presentation: Hilton Hawaian Village, Hawaii. USA
  • Year and Date: 2012-06-29
• [Presentation] The role of salivary glands in phosphate homeostasis (2012)
  • Author(s): Mukai T, Segawa H, Sasaki S, Ohnishi S, Ishikawa Y, Horiba N, Ueda O, Jishage K, Fukushima N, Kido S, Miyamoto K
  • Organizer: XVI International Congress on Nutrition and Metabolism in Renal Disease
  • Place of Presentation: Hilton Hawaian Village, Hawaii, USA
  • Year and Date: 2012-06-29
• [Presentation] Muscle atrophy in patients with CKD results from FGF23/Klotho-mediated suppression of Insulin/IGF-I signaling (2012)
  • Author(s): Kido S, Hashimoto Y, Segawa H, Tatsumi S, Miyamoto K
  • Organizer: XVI International Congress on Nutrition and Metabolism in Renal Disease
  • Place of Presentation: Hilton Hawaian Village, Hawaii, USA.
  • Year and Date: 2012-06-27
• [Presentation] 生体内リン代謝調節機構における唾液腺の関与 (2012)
  • Author(s): 向井朋、瀬川博子、宮本賢一
  • Organizer: 第66回日本栄養・食糧学会大会
  • Place of Presentation: 東北大学、宮城県
  • Year and Date: 2012-05-19
• [Presentation] ナトリウム依存性リン酸トランスポーターNpt2bの新たな生理機能の解明 (2012)
  • Author(s): 向井朋、瀬川博子、宮本賢一
  • Organizer: 病態栄養学会
  • Place of Presentation: 国際会議場、京都府
  • Year and Date: 2012-01-14
• [Presentation] Post-Hepatectomy Hypophosphatemia in Rats (2011)
  • Author(s): Nomura K, Tatsumi S, Shiozaki Y, Yamaguchi S, Kamatani T, Segawa H, Kido S, Miyamoto K
  • Organizer: The American Society of Nephrology Annual Meeting
  • Place of Presentation: Pennsylvania Convention Center, PA, USA
  • Year and Date: 2011-11-11
• [Presentation] Role of Sodium-Dependent Phosphate (Pi) Transporter (Npt2b) on Salivary Pi Secretion (2011)
  • Author(s): Segawa H, Mukai T, Ohnishi S, Sasaki S, Ohi A, Kuwahara S, Kido S, Tatsumi S, Ishikawa Y, Ueda O, Horiba N, Jishage K, Fukushima N, Miyamoto K
  • Organizer: The American Society of Nephrology Annual Meeting
  • Place of Presentation: Pennsylvania Convention Center, PA, USA
  • Year and Date: 2011-11-11
• [Presentation] Molecular Consequences of the SLC34A3 Mutations of Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) (2011)
  • Author(s): Ohi A, Haito-Sugino S, Ito M, Shiozaki Y, Nomura K, Kusaka Y, Sasaki S, Ohnishi S, Yamaguchi S, Kiso S, Tatsumi S, Segawa H, Miyamoto K
  • Organizer: The American Society of Nephrology Annual Meeting
  • Place of Presentation: Pennsylvania Convention Center, PA, USA
  • Year and Date: 2011-11-11
• [Presentation] ナトリウム依存性リン酸トランスポーターNpt2bの新たな生理機能の解明 (2011)
  • Author(s): 向井朋、瀬川博子、宮本賢一
  • Organizer: 第41回日本腎臓学会東西学術集会西部大会
  • Place of Presentation: あわぎんホール、徳島
  • Year and Date: 2011-10-01
• [Presentation] リン酸トランスポーターと慢性腎臓病 (2011)
  • Author(s): 瀬川博子
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜、神奈川県
  • Year and Date: 2011-06-15