Identification and functional analysis of regulatory factors for fibroblast growth factor 23/klotho/inorganic sensor system
| Project/Area Number |
20390236
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | The University of Tokushima |
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Principal Investigator |
MIYAMOTO Kenichi The University of Tokushima, 大学院・ヘルスバイオサイエンス研究部, 教授 (70174208)
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| 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)
TATSUMI Sawako 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (80420545)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2010: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2009: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2008: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
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| Keywords | リン / 腎臓 / トランスポーター / 副甲状腺ホルモン / 骨 / 低リン血症 / クル病 / 腸管 / クロライド / ノックアウトマウス / ビタミンD / 肝臓 / グルコース / 腎総 |
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| Research Abstract |
In the present study, we investigated inorganic phosphate (Pi) metabolism in the type IIa and type IIc sodium-dependent Pi cotransporter gene knockout mice (Npt2a^<-/->Npt2c>^<-/-> DKO mice). To clarify the relative importance of Npt2a and Npt2c, we studied DKO mice These mice exhibited severe hypophosphatemia, hypercalciuria, and rickets. This phenotype is similar to that seen inhereditary hypophosphatemic rickts with hypercalciuria (HHRH) which is characterized by hypophosphate, short stature, rickets, and/or osteomalacia, with secondary absorptive hypercalciuria. Studies of the DKO animals showed that the expansion of the late hypertrophic zone in the bone, which is a characteristic feature of rickets, might be secondary to the impaired apoptosis of these cells. In the analysis of DNA microarray in the kidney of DKO mice, we identified the clone encode calcium activated chloride channel 6 (CLCA6) and analyzed its function in Xenopus oocytes and renal epithelial cells. The present study indicates that CLCA6 modulates the activity of type III renal sodium-dependent Pi cotransporter PiT2 in DKO mice.
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Report
(4 results)
Research Products
(136 results)
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[Journal Article] Sodium-dependent phosphate cotransporters : Lessons from gene knockout and mutation studies.2011
Author(s)
Miyamoto KI, Haito-Sugino S, Kuwahara S, Ohi A, Nomura K, Ito M, Kuwahata M, Kido S, Tatsumi S, Kaneko I, Segawa H.
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Journal Title
J Pharm Sci. doi:10.1002/jps.22614.
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Peer Reviewed
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[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.
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Journal Title
Pflugers Arch. 461(1)
Pages: 77-90
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Peer Reviewed
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[Journal Article] An apical expression signal of the renal type IIc Na+-dependent phosphate cotransporter in renal epithelial cells.2010
Author(s)
Ito M, Sakurai A, Hayashi K, Ohi A, Kangawa N, Nishiyama T, Sugino S, Uehata Y, Kamahara A, Sakata M, Tatsumi S, Kuwahata M, Taketani Y, Segawa H, Miyamoto KI.
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Journal Title
Am J Phisiol Renal Phisiol. 299(1)
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Peer Reviewed
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[Journal Article] Phosphaturic action of fibroblast growth factor 23 in Npt2 null mice.2010
Author(s)
Tomoe Y, Segawa H, Shiozawa K, Kaneko I, Tominaga R, Hanabusa E, Aranami F, Furutani J, Kuwahara S, Tatsumi S, Matsumoto M, Ito M, Miyamoto KI.
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Journal Title
Am J Physiol Renal Physiol. 298(6)
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Peer Reviewed
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[Journal Article] Regulation of renal sodium-dependent phosphate cotransporter genes (Npt2a and Npt2c) by all-trans-retinoic acid and its receptors.2010
Author(s)
Masuda M, Yamamoto H, Kozai M, Tanaka S, Ishiguro M, Takei Y, Nakahashi O, Ikeda S, Uebanso T, Taketani Y, Segawa H, Miyamoto KI, Takeda E.
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Journal Title
Biochem J. 429(3)
Pages: 583-592
Related Report
Peer Reviewed
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[Journal Article] Thyroid hormones regulate phosphate homoeostasis through transcriptional control of the renal type IIa sodium-dependent phosphate co-transporter (Npt2a) gene.2010
Author(s)
Ishiguro M, Yamamoto H, Masuda M, Kozai M, Takei Y, Tanaka S, Sato T, Segawa H, Taketani Y, Arai H, Miyamoto K, Takeda E.
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Journal Title
Biochem J. 427(1)
Pages: 161-169
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Peer Reviewed
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[Journal Article] Npt2a and Npt2c in mice play distinct and synergistic roles in inorganic phosphate metabolism and skeletal development.2009
Author(s)
Segawa H, Onitsuka A, Furutani J, Kaneko I, Aranami F, Matsumoto N, Tomoe Y, Kuwahata M, Ito M, Matsumoto M, Li M, Amizuka N, Miyamoto K.
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Journal Title
Am J Physiol Renal Physiol. 297(3)
Related Report
Peer Reviewed
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[Journal Article] Differential regulation of the renal sodium-phosphate cotransporters NaPi-IIa, NaPi-IIc, and PiT-2 in dietary potassium deficiency.2009
Author(s)
Breusegem SY, Takahashi H, Giral-Arnal H, Wang X, Jiang T, Verlander JW, Wilson P, Miyazaki-Anzai S, Sutherland E, Caldas Y, Blaine JT, Segawa H, Miyamoto K, Barry NP, Levi M.
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Journal Title
Am J Physiol Renal Physiol. 297(2)
Related Report
Peer Reviewed
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[Journal Article] Type 11c sodium- dependent phosphate transporter regulates calcium metabolism.2009
Author(s)
Segawa H, Onitsuka A, Kuwahata M, Hanabusa E, Furutani J, Kaneko I, Tomoe Y, Aranami H, Matsumoto M, Li M, Amizuka N, Miyamoto K.
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Journal Title
J Am Nephrol. 20(1)
Pages: 104-113
Related Report
Peer Reviewed
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[Journal Article] Polypyrimidine tract-binding protein is involved in regulation of albumin synthesis in response to food intake.2008
Author(s)
Kuwahata M, Kuramoto Y, Sawai Y, Amano S, Tomoe Y, Segawa H, Tatsumi S, Ito M, Kobayashi Y, Kido Y, Oka T, Miyamoto K.
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Journal Title
J Nutr Sci Vitaminol. 54(2)
Pages: 142-147
NAID
Related Report
Peer Reviewed
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[Presentation] Phosphate Homeostasis in Osteocyte-Ablated Mice.2010
Author(s)
Tatsumi S, Yamaguchi S,Kamatani T, Shiozaki Y, Nomura K, Saito Y, Kido S, Segawa H, Miyamoto K.
Organizer
The American Society of Nephrology. Colorado Convention Center
Place of Presentation
Denver, CO, USA.
Year and Date
2010-11-18
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[Presentation] リンの話題2010
Author(s)
宮本賢一
Organizer
第33回栃木県透析医学会
Place of Presentation
とちぎ健康の森(宇都宮)
Year and Date
2010-09-11
Related Report
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[Presentation] 腸管とリン代謝2010
Author(s)
宮本賢一
Organizer
第28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)
Year and Date
2010-07-22
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[Presentation] Inorganic Phosphate Homeostasis in the Type 1 Na/Pi-transporter(NPT1)Null Mice.2009
Author(s)
Segawa H, Sawai Y, Tominaga R, Hanabusa E,Kuwahara S, Aranami F, Furutani J, Kaneko I, Kuroiwa Y, Kisuhara H,Sugiyama Y, Miyamoto K.
Organizer
The American Society of Nephrology. San Diego Convention Center.
Place of Presentation
San Diego, CA, USA.
Year and Date
2009-10-30
Related Report
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[Presentation] klotho Modulates the Activity of Type 11c Na+-Dependent Phosphate Cotransporter (NaPi-11c) in Renal Epithelial Cells.2009
Author(s)
Nishiyama T, Ito M, Ohi A,Sugino S, Kaneko I,Sakata M,Kamahara A, Kido S, Tatsumi S, Segawa H, Miyamoto K.
Organizer
The American Society of Nephrology. San Diego Convention Center.
Place of Presentation
San Diego, CA, USA.
Year and Date
2009-10-30
Related Report
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[Presentation] Characterization of Phosphate Metabolism in the NaPi-11b Hetero Knockout Mice.2009
Author(s)
Hanabusa E, Ueda O, Segawa H, Kaneko I, Kuwahara S, Tatsumi S, Ohtomo S, Horiba N, Tachibe T, Wada N, Kawase Y, Jishage K, Fukushima N, Miyamoto K
Organizer
The American Society of Nephrology San Diego Convention Center
Place of Presentation
San Diego, CA, USA.
Year and Date
2009-10-30
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[Presentation] Mutation of Type IIc Na+- Dependent Phosphate Cotransporter (NaPi-IIc) and Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) The American Society of Nephrology.2008
Author(s)
Ito M, Sakurai A, Ohi A, Hayashi K, Nishiyama T, Kangawa N, Sugino S, Tatsumi S, Segawa H, Miyamoto K.
Organizer
Pennsylvania Convention Center
Place of Presentation
Philadelphia, Pennsylvania, USA.
Year and Date
2008-11-07
Related Report
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[Presentation] Effect of Fibroblast Growth Factor (FGF) 23 on Npt2a, Npt2c Double-Knockout (WKO) Mice.2008
Author(s)
Tomoe Y, Segawa H,Kaneko I, Furutani J, Aranami F, Kuwahara S, Tominaga R, Hanabusa E, Ito M, Miyamoto K.
Organizer
The American Society of Nephrology. Pennsylvania Convention Center
Place of Presentation
Philadelphia, Pennsylvania, USA.
Year and Date
2008-11-07
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