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2013 Fiscal Year Final Research Report

Signal networks among organ/tissue in the disorder of phosphate homeostasis

Research Project

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Project/Area Number 23390226
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionThe University of Tokushima

Principal Investigator

MIYAMOTO KENICHI  徳島大学, ヘルスバイオサイエンス研究部, 教授 (70174208)

Co-Investigator(Kenkyū-buntansha) SEGAWA Hiroko  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 講師 (70325257)
KIDO Shinsuke  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 特任助教 (30437652)
Project Period (FY) 2011-04-01 – 2014-03-31
Keywordsリン利尿 / 腎臓 / 繊維芽細胞増殖因子23 (FGF23) / 骨細胞
Research Abstract

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays an important role in phosphate (Pi) transport in the proximal tubular cells. Klotho forms a specific receptor complex with FGF receptor that transmits signaling of FGF23 in the distal tubules. FGF23/klotho signaling leads to down-regulation of sodium-dependent Pi cotransporter (NaPi-II ) in the proximal tubules. In the present study, we investigated the mechanisms of down-regulation of renal Pi transporter by FGF23/klotho system and the production of FGF23 in bone cells. We show that klotho expression in the proximal tubules is induced by several conditions. Furthermore, inactivation of NaPi-IIc by PKC is the first step of FGF23/klotho dependent down-regulation of the transporters. Thus, FGF23/klotho signaling in the kidney-bone axis is essential for Pi homeostasis.

  • Research Products

    (40 results)

All 2014 2013 2012 2011

All Journal Article (29 results) (of which Peer Reviewed: 29 results) Presentation (11 results)

  • [Journal Article] Cardiac remodeling associated with protein increase and lipid accumulation in early-stage chronic kidney disease in rats2014

    • Author(s)
      Kuwahara M, Bannai K, Segawa H, Miyamoto K, Yamato H
    • Journal Title

      Biochim Biophys Acta

      Volume: 4439(14) Pages: 00113-00116

    • DOI

      10.1016/j.bbadis.2014.04.026

    • Peer Reviewed
  • [Journal Article] Molecular Mechanisms of Cadmium-Induced Fibroblast growth Factor 23 Upregulation in Osteoblast-Like Cells2014

    • Author(s)
      Kido S, Fujihara M, Nomura K, Sasaki S(他8名)
    • Journal Title

      Toxicol Sci. Jun

      Volume: 139(2) Pages: 301-316

    • DOI

      10.1093/toxsci/kfu043

    • Peer Reviewed
  • [Journal Article] Effect of dietary components on renal inorganic phosphate (Pi) excretion induced by a Pi-depleted diet2014

    • Author(s)
      Ohnishi R, Segawa H, Ohmoto T, Sasaki S(他8名)
    • Journal Title

      J Med Invest

      Volume: 61(1.2) Pages: 162-170

    • URL

      https://www.jstage.jst.go.jp/browse/jmi/61/0/_contents

    • Peer Reviewed
  • [Journal Article] Down-regulation of renal type IIa sodium-dependent phosphate co-transporter during lipopolysaccharide-induced acute inflammation2014

    • Author(s)
      Ikeda S, Yamamoto H, Masuda M, Miyamoto K(他9名)
    • Journal Title

      Am J Physiol Renal Physiol

      Volume: 306(7) Pages: 744-750

    • DOI

      10.1152/ajprenal.00474.2013

    • Peer Reviewed
  • [Journal Article] Short-term dietary phosphate restriction up-regulates ileal fibroblast growth factor 15 gene expression in mice2014

    • Author(s)
      Nakahashi O, Yamamoto H, Miyamoto K(他8名)
    • Journal Title

      J Clin Biochem Nutr

      Volume: 54(2) Pages: 102-108

    • DOI

      10.3164/jcbn.13-109

    • Peer Reviewed
  • [Journal Article] Hepatectomy-Related Hypophosphatemia : A Novel Phosphaturic Factor in the Liver-Kidney Axis2014

    • Author(s)
      Nomura K, Tatsumi S, Miyamoto K(他10名)
    • Journal Title

      J Am Soc Nephrol

      Volume: vol.25, No.4 Pages: 761-772

    • DOI

      10.1681/ASN.2013060569

    • Peer Reviewed
  • [Journal Article] Hypercholesterolemia and effects of high cholesterol diet in type IIa sodium-dependent phosphate co-transporter (Npt2a) deficient mice2013

    • Author(s)
      Tanaka S, Yamamoto H, Miyamoto K(他8名)
    • Journal Title

      J Med Invest

      Volume: 60(3.4) Pages: 191-196

    • URL

      https://www.jstage.jst.go.jp/browse/jmi/60/3.4/_contents

    • Peer Reviewed
  • [Journal Article] Ferric citrate hydrate, a new phosphate binder, prevents the complications of secondary hyperparathyroidism and vascular calcification2013

    • Author(s)
      Iida A, Kemmochi Y, Miyamoto K(他7名)
    • Journal Title

      Am J Nephrol

      Volume: 37 Pages: 346-358

    • DOI

      10.1159/000348805

    • Peer Reviewed
  • [Journal Article] Vitamin D and type II sodium-dependent phosphate cotransporters. Contrib Nephrol2013

    • Author(s)
      Kido S, Kaneko I, Tatsumi S, Segawa H, Miyamoto K
    • Journal Title

      Contrib Nephrol

      Volume: 180 Pages: 86-97

    • DOI

      10.1159/000346786

    • 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 cells2013

    • Author(s)
      Yamada F, Horie D, Miyamoto K(他7名)
    • Journal Title

      J Med Invest

      Volume: 60(1.2) Pages: 27-34

    • URL

      https://www.jstage.jst.go.jp/browse/jmi/60/1.2/_contents

    • Peer Reviewed
  • [Journal Article] Parathyroid hormone (1-34) counteracts the suppression of interleulin-11 expression by glucocorticoid in murine osteoblasts : a possible mechanism for stimulating osteoblast differentiation against glucocorticoid excess2013

    • Author(s)
      Kuriwaka-Kido R, Kido S, Miyatani Y(他7名)
    • Journal Title

      Endocrinology

      Volume: 154 Pages: 1156-1167

    • DOI

      10.1210/en.2013-1915

    • Peer Reviewed
  • [Journal Article] Evaluation of 14 questions detecting malnutrition in newly hospitalized patients2013

    • Author(s)
      Kayashita A, Yamato H, Yoshida I, Matsuzaki K, Niki H, Nagae H, Miyamoto K
    • Journal Title

      J Med Invest

      Volume: 60(1.2) Pages: 138-145

    • URL

      https://www.jstage.jst.go.jp/browse/jmi/60/1.2/_contents

    • Peer Reviewed
  • [Journal Article] Ezrin, a membrane cytoskeletal cross-linker, is essential for the regulation of phosphate and calcium homeostasis2013

    • Author(s)
      Hatano R, Fujii E, Segawa H(他6名)
    • Journal Title

      Kidney Int

      Volume: 83(1) Pages: 41-49

    • DOI

      10.1038/ki.2012

    • Peer Reviewed
  • [Journal Article] Critical role of parathyroid hormone (PTH) receptor-1 phosphorylation in regulating acute response to PTH2013

    • Author(s)
      Maeda A, Okazaki M, Baron DM, Dean T, Khatri A, Mahon M, Segawa H, Abou-Samra AB, Jüppner H, Bloch KD, Potts JT Jr, Gardella TJ
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 110 Pages: 5864-5869

    • DOI

      10.1073/pnas.1301674110

    • 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 mice2013

    • Author(s)
      Guo J, Song L, Liu M, Segawa H, Miyamoto K, Bringhurst FR, Kronenberg HM, Jüppner 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 PepT12013

    • Author(s)
      Furutani J, Segawa H, Miyamoto K(他6名)
    • Journal Title

      J Ren Nutr

      Volume: 23(2) Pages: e11-20

    • DOI

      10.1053/j.jrn.2012.02.006

    • Peer Reviewed
  • [Journal Article] Identification and functional analysis of a splice variant of mouse sodium-dependent phosphate transporter Npt2c2012

    • Author(s)
      Kuwahara S, Aranami F, Segawa H(他13名)
    • Journal Title

      J Med Invest

      Volume: 59(1.2) Pages: 116-126

    • URL

      https://www.jstage.jst.go.jp/browse/jmi/59/1,2/_contents

    • Peer Reviewed
  • [Journal Article] Processing and stability of type IIc sodium-dependent phosphatre cotransporter mutations in patients with hereditary hypophosphatemia rickets with hypercalciuria2012

    • Author(s)
      Haito-Sugino S, Ito M, Ohi A, Miyamoto K(他9名)
    • Journal Title

      Am J Physiol Cell Physiol

      Volume: 302 Pages: C1316-1330

    • DOI

      10.1152/ajpcell.00314.2011

    • Peer Reviewed
  • [Journal Article] Dietary phosphate restriction ameliorates endothelial dysfunction in adenine-induced kidney disease rats2012

    • Author(s)
      Van TV, Watari E, Taketani Y, Miyamoto K(他8名目)
    • Journal Title

      J Clin Biochem Nutr

      Volume: 51(1) Pages: 27-32

    • DOI

      10.3164/jcbn.11-96

    • Peer Reviewed
  • [Journal Article] Clinical consequences of mutations in sodium phosphate cotransporters2012

    • Author(s)
      Lederer E and Miyamoto K
    • Journal Title

      Clin J Am Soc Nephrol

      Volume: 7(7) Pages: 1179-1187

    • DOI

      10.2215/CJN.09090911

    • Peer Reviewed
  • [Journal Article] Regulation of osteoblast differentiation by interleukin-11 via AP-1 and Smad signaling2012

    • Author(s)
      Matsumoto T, Kuriwaka-Kido R, Kondo T, Endo I, Kido S
    • Journal Title

      Endocr J

      Volume: 59(2) Pages: 91-101

    • DOI

      10.1507/endocrj.EJ11-0219

    • Peer Reviewed
  • [Journal Article] Inorganic phosphate homeostasis in sodium-dependent phosphate co-transporter Npt2b+/- mice2011

    • Author(s)
      Ohi A, Hanabusa E, Ueda O, Segawa H(他21名)
    • Journal Title

      Am J Physiol Renal Physiol

      Volume: 301 Pages: F1105-F1113

    • DOI

      10.1152/ajprenal.00663.2010

    • Peer Reviewed
  • [Journal Article] Accumulation of orally administered quercetin in brain tissue and its antioxidative effects in rats2011

    • Author(s)
      Ishisaka A, Ichikawa S, Miyamoto K(他8名)
    • Journal Title

      Free Radic Biol Med

      Volume: 51(7) Pages: 1329-1336

    • DOI

      10.1016/j.freeradbiomed.2011.06.017

    • Peer Reviewed
  • [Journal Article] Dietary medium-chain triglycerides attenuate hepatic lipid deposition in growing rats with protein malnutrition2011

    • Author(s)
      Kuwahata M, Kubota H, Miyamoto K(他7名)
    • Journal Title

      J Nutr Sci Vitaminol (Tokyo)

      Volume: 57(2) Pages: 138-43

    • DOI

      10.3177/jnsv.57.138

    • Peer Reviewed
  • [Journal Article] Sodium-dependent phosphate cotransporters : Lessons from gene knockout and mutation studies2011

    • 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(9) Pages: 3719-3730

    • DOI

      10.1002/jps.22614

    • Peer Reviewed
  • [Journal Article] Transgenic overexpression of the extra-large Gsα variant XLαs enhances Gsα-mediated responses in the mouse renal proximal tubule in vivo2011

    • Author(s)
      Liu Z, Segawa H, Aydin C, Reyes M, Erben RG, Weinstein LS, Chen M, Marshansky V, Fröhlich LF, Bastepe M
    • Journal Title

      Endocrinology

      Volume: 152 Pages: 1222-1233

    • DOI

      10.1210/en.2010-1034

    • Peer Reviewed
  • [Journal Article] Analysis of different complexes of type IIa sodium-dependent phosphate transporter in rat renal cortex using blue-native polyacrylamide gel electrophoresis2011

    • Author(s)
      Tanimura A, Yamada F, Saito A, Ito M, Kimura T, Anzai N, Horie D, Yamamoto H, Miyamoto K, Taketani Y, Takeda E
    • Journal Title

      J Med Invest

      Volume: 58(1.2) Pages: 140-147

    • URL

      https://www.jstage.jst.go.jp/browse/jmi/58/1,2/_contents

    • Peer Reviewed
  • [Journal Article] Source matters : from phosphorus load to bioavailability2011

    • Author(s)
      Fukagawa M, Komaba H, Miyamoto K
    • Journal Title

      Clin J Am Soc Nephrol

      Volume: 6 : (2) Pages: 239-240

    • DOI

      10.2215/CJN.11051210

    • 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 analogs2011

    • Author(s)
      Nagai S, Okazaki M, Segawa H, Bergwitz C, Dean T, Potts JT Jr, Mahon MJ, Gardella TJ, Jüppner H
    • Journal Title

      J. Biol. Chem

      Volume: 286 Pages: 1618-1626

    • DOI

      10.1074/jbc.M110.198416

    • Peer Reviewed
  • [Presentation] Hepatectomy Hypophosphatemia : A Novel Phosphaturic Factor in the Liver Kidney Axis2013

    • Author(s)
      Nomura K, Tatsumi S, Miyagawa A, Shiozaki Y, Sasaki S, Segawa H, Miyamoto K
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      GeorgiaWorldCongressCenter, Atlanta, GA, USA
    • Year and Date
      2013-11-08
  • [Presentation] Molecular mechanisms of cadmium (Cd) dependent fibroblast growth factor 23 secretion in bone2012

    • Author(s)
      Kido S, Fujiwara M, Nomura K, Sasaki S, Shiozaki Y, Segawa H, Tatsumi S, Miyamoto K
    • Organizer
      Americal Society Nephrology, Kidney Week
    • Place of Presentation
      San Diego Convention Center, CA, USA
    • Year and Date
      2012-11-02
  • [Presentation] Mechanisms of hyperphosphatemia in the osteocyte-abelated mice2012

    • Author(s)
      Tatsumi S, Kamatani T, Nomura K, Yoshimi A, Shiozaki Y, Sasaki S, Manabe M, Kido S, Segawa H, Miyamoto K
    • Organizer
      Americal Society Nephrology, Kidney Week
    • Place of Presentation
      San Diego Convention Center, CA, USA
    • Year and Date
      2012-11-02
  • [Presentation] Clinical consequences of gene mutations involved in renal phosphate transport2012

    • 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] The role of salivary glands in phosphate homeostasis2012

    • Author(s)
      Mukai T, Segawa H, Sasaki S, (他9名)
    • Organizer
      XVI International Congress on Nutrition and Metabolism in Renal Disease
    • Place of Presentation
      Hilton Hawaian Village, Honolulu, Hawaii, USA
    • Year and Date
      2012-06-29
  • [Presentation] Dietary inorganic phosphorus and intestinal peptide absorption2012

    • 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, Honolulu, 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 signaling2012

    • 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, Honolulu, Hawaii, USA
    • Year and Date
      2012-06-27
  • [Presentation] Phosphorus Management and Clinical Outcomes2012

    • Author(s)
      Miyamoto K
    • Organizer
      XVI International Congress on Nutrition and Metabolism in Renal Disease
    • Place of Presentation
      Hilton Hawaian Village, Honolulu, Hawaii, USA
    • Year and Date
      2012-06-26
  • [Presentation] Post-Hepatectomy Hypophosphatemia in Rats2011

    • Author(s)
      Nomura K, Tatsumi S, Shiozaki Y, Yamaguchi S, Kamatani T, Segawa H, Kido S, Miyamoto K
    • Organizer
      J Am Soc Nephrol
    • Place of Presentation
      Pennsylvania Convention Center in Philadelphia, USA
    • Year and Date
      2011-11-12
  • [Presentation] Role of Sodium-Dependent Phosphate(Pi)Transporter(Npt2b)on Salivary Pi Secretion2011

    • 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
      J Am Soc Nephrol
    • Place of Presentation
      Pennsylvania Convention Center in Philadelphia, 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, Kido S, Tatsumi S, Segawa H, Miyamoto K
    • Organizer
      J Am Soc Nephrol
    • Place of Presentation
      Pennsylvania Convention Center in Philadelphia, USA
    • Year and Date
      2011-11-10

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Published: 2015-06-25  

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