Fibroblast growth factor 23 mediates the phosphaturic actions of cadmium

Phosphaturia has been documented following cadmium (Cd) exposure in both humans and experimental animals. The fibroblast growth factor 23 (FGF23)/klotho axis serves as an essential phosphate homeostasis pathway in the bone-kidney axis. In the present study, we investigated the effects of Cd on phosp...

Full description

Saved in:
Bibliographic Details
Published inThe Journal of Medical Investigation Vol. 57; no. 1,2; pp. 95 - 108
Main Authors Furutani, Junya, Ito, Mikiko, Kuwahara, Shoji, Hanabusa, Etsuyo, Miyamoto, Ken-ichi, Tominaga, Rieko, Aranami, Fumito, Kido, Shinsuke, Tatsumi, Sawako, Segawa, Hiroko
Format Journal Article
LanguageEnglish
Published Japan The University of Tokushima Faculty of Medicine 2010
Subjects
Animals
cadmium
Cadmium - toxicity
Extracellular Matrix Proteins - genetics
Female
FGF23
Fibroblast Growth Factors - genetics
Fibroblast Growth Factors - physiology
Hypophosphatemia, Familial - chemically induced
Mice
Mice, Inbred C57BL
Mice, Knockout
PHEX Phosphate Regulating Neutral Endopeptidase - genetics
phosphate
proximal tubule
RNA, Messenger - analysis
Sodium-Phosphate Cotransporter Proteins, Type IIa - analysis
Sodium-Phosphate Cotransporter Proteins, Type IIa - physiology
transporter
Online AccessGet full text
ISSN1343-1420
1349-6867
DOI10.2152/jmi.57.95

Cover

Abstract Phosphaturia has been documented following cadmium (Cd) exposure in both humans and experimental animals. The fibroblast growth factor 23 (FGF23)/klotho axis serves as an essential phosphate homeostasis pathway in the bone-kidney axis. In the present study, we investigated the effects of Cd on phosphate (Pi) homeostasis in mice. Following Cd injection into WT mice, plasma FGF23 concentration was significantly increased. Urinary Pi excretion levels were significantly higher in Cd-injected WT mice than in control group. Plasma Pi concentration decreased only slightly compared with control group. No change was observed in plasma parathyroid hormone and 1,25-dihydroxy vitamin D3 in both group of mice. We observed a decrease in phosphate transport activity and also decrease in expression of renal phosphate transporter SLC34A3 [NaPi-IIc/NPT2c], but not SLC34A1 [NaPi-IIa/NPT2a]. Furthermore, we examined the effect of Cd on Npt2c in Npt2a-knockout (KO) mice which expresses Npt2c as a major NaPi co-transporter. Injecting Cd to Npt2aKO mice induced significant increase in plasma FGF23 concentration and urinary Pi excretion levels. Furthermore, we observed a decrease in phosphate transport activity and renal Npt2c expression in Cd-injected Npt2a KO mice. The present study suggests that hypophosphatemia induced by Cd may be closely associated with the FGF23/klotho axis. J. Med. Invest. 57: 95-108, February, 2010
AbstractList Phosphaturia has been documented following cadmium (Cd) exposure in both humans and experimental animals. The fibroblast growth factor 23 (FGF23)/klotho axis serves as an essential phosphate homeostasis pathway in the bone-kidney axis. In the present study, we investigated the effects of Cd on phosphate (Pi) homeostasis in mice. Following Cd injection into WT mice, plasma FGF23 concentration was significantly increased. Urinary Pi excretion levels were significantly higher in Cd-injected WT mice than in control group. Plasma Pi concentration decreased only slightly compared with control group. No change was observed in plasma parathyroid hormone and 1,25-dihydroxy vitamin D(3) in both group of mice. We observed a decrease in phosphate transport activity and also decrease in expression of renal phosphate transporter SLC34A3 [NaPi-IIc/NPT2c], but not SLC34A1 [NaPi-IIa/NPT2a]. Furthermore, we examined the effect of Cd on Npt2c in Npt2a-knockout (KO) mice which expresses Npt2c as a major NaPi co-transporter. Injecting Cd to Npt2aKO mice induced significant increase in plasma FGF23 concentration and urinary Pi excretion levels. Furthermore, we observed a decrease in phosphate transport activity and renal Npt2c expression in Cd-injected Npt2a KO mice. The present study suggests that hypophosphatemia induced by Cd may be closely associated with the FGF23/klotho axis.
Phosphaturia has been documented following cadmium (Cd) exposure in both humans and experimental animals. The fibroblast growth factor 23 (FGF23)/klotho axis serves as an essential phosphate homeostasis pathway in the bone-kidney axis. In the present study, we investigated the effects of Cd on phosphate (Pi) homeostasis in mice. Following Cd injection into WT mice, plasma FGF23 concentration was significantly increased. Urinary Pi excretion levels were significantly higher in Cd-injected WT mice than in control group. Plasma Pi concentration decreased only slightly compared with control group. No change was observed in plasma parathyroid hormone and 1,25-dihydroxy vitamin D3 in both group of mice. We observed a decrease in phosphate transport activity and also decrease in expression of renal phosphate transporter SLC34A3 [NaPi-IIc/NPT2c], but not SLC34A1 [NaPi-IIa/NPT2a]. Furthermore, we examined the effect of Cd on Npt2c in Npt2a-knockout (KO) mice which expresses Npt2c as a major NaPi co-transporter. Injecting Cd to Npt2aKO mice induced significant increase in plasma FGF23 concentration and urinary Pi excretion levels. Furthermore, we observed a decrease in phosphate transport activity and renal Npt2c expression in Cd-injected Npt2a KO mice. The present study suggests that hypophosphatemia induced by Cd may be closely associated with the FGF23/klotho axis. J. Med. Invest. 57: 95-108, February, 2010
Author Ito, Mikiko
Hanabusa, Etsuyo
Furutani, Junya
Tatsumi, Sawako
Aranami, Fumito
Kuwahara, Shoji
Miyamoto, Ken-ichi
Segawa, Hiroko
Kido, Shinsuke
Tominaga, Rieko
Author_xml – sequence: 1
  fullname: Furutani, Junya
  organization: Deprtment of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School
– sequence: 1
  fullname: Ito, Mikiko
  organization: School of Human Science and Environment, University of Hyogo
– sequence: 1
  fullname: Kuwahara, Shoji
  organization: Deprtment of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School
– sequence: 1
  fullname: Hanabusa, Etsuyo
  organization: Deprtment of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School
– sequence: 1
  fullname: Miyamoto, Ken-ichi
  organization: Deprtment of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School
– sequence: 1
  fullname: Tominaga, Rieko
  organization: Deprtment of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School
– sequence: 1
  fullname: Aranami, Fumito
  organization: Deprtment of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School
– sequence: 1
  fullname: Kido, Shinsuke
  organization: Deprtment of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School
– sequence: 1
  fullname: Tatsumi, Sawako
  organization: Deprtment of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School
– sequence: 1
  fullname: Segawa, Hiroko
  organization: Deprtment of Molecular Nutrition, Institution of Health Biosciences, University of Tokushima Graduate School
BackLink https://www.ncbi.nlm.nih.gov/pubmed/20299748$$D View this record in MEDLINE/PubMed
BookMark eNptkEtPwzAQhC0Eog848AeQrxzS-pk0R6goRarEBc7W2nEaV3nJdoX496SU9oA4zUrz7WhnJ-iy7VqL0B0lM0Ylm-8aN5PZLJcXaEy5yJN0kWaXPzNPqGBkhCYh7AjhXEp5jUaMsDzPxGKM1iunfadrCBFvffcZK1yCiZ3HjOPGFg6iDThWFvdVF_oK4t47gwfEdW3AXYkNFI3bNzfoqoQ62NtfnaKP1fP7cp1s3l5el4-bxMhsERMKqRCpIJKK0gBYKHWaEl1QxqEwRaHtwAnDmLapZqSkLBOFyXQuitIOLp-i-2Nuv9fDfar3rgH_pU6VBuDhCBjfheBteUYoUYd3qeFdSmYqlwM7_8MaF-FQLXpw9b8bT8eNXYiwteds8NGZ2p5IqthJcnk2TQVe2ZZ_A3CEhpw
CitedBy_id crossref_primary_10_1186_s12014_019_9231_7
crossref_primary_10_1016_j_ecoenv_2024_116101
crossref_primary_10_1002_biof_1376
crossref_primary_10_1093_toxsci_kfu043
crossref_primary_10_4103_jfmpc_jfmpc_1836_23
crossref_primary_10_1080_10937404_2020_1860842
crossref_primary_10_53518_mjavl_1196166
crossref_primary_10_1002_1873_3468_13494
crossref_primary_10_1016_j_bone_2013_01_011
crossref_primary_10_1016_j_marpolbul_2021_113007
crossref_primary_10_34172_apb_2020_023
crossref_primary_10_3390_nu11040849
Cites_doi 10.1146/annurev.nutr.25.050304.092642
10.1074/jbc.C500457200
10.1210/en.2005-0777
10.1007/s00424-008-0580-8
10.1016/0041-008X(92)90066-2
10.1006/taap.1993.1134
10.1073/pnas.101545198
10.1172/JCI36479
10.1152/ajprenal.00156.2009
10.1359/jbmr.2000.15.8.1579
10.1016/j.tox.2004.06.005
10.1074/jbc.M200943200
10.1038/81664
10.1042/BJ20041799
10.1007/s00424-003-1084-1
10.1007/s00467-009-1260-4
10.1007/s00774-007-0776-6
10.1073/pnas.95.9.5372
10.1007/s10875-009-9277-9
10.1006/taap.1997.8180
10.1359/JBMR.0301264
10.2170/jjphysiol.54.93
10.1016/j.bone.2008.02.014
10.1507/endocrj.45.431
10.1086/499410
10.1152/ajprenal.90765.2008
10.1681/ASN.2008020177
10.1006/taap.1995.1147
10.1111/j.1600-0773.1988.tb00966.x
10.1016/j.bone.2003.12.002
10.2302/kjm.18.181
10.1016/S0278-6915(97)00068-9
10.1152/ajprenal.90538.2008
10.1152/ajprenal.00097.2004
10.1007/s004240050141
10.1016/S0140-6736(98)09356-8
10.1152/ajprenal.00252.2003
10.1210/jc.2008-2396
10.1016/0378-4274(91)90123-N
10.1152/ajprenal.00248.2006
10.1016/j.bone.2009.06.017
10.1159/000107069
10.1086/499409
10.1097/MNH.0b013e328331a8c8
10.1016/j.mce.2008.10.052
10.1007/BF00377675
ContentType Journal Article
Copyright 2010 by The University of Tokushima Faculty of Medicine
Copyright_xml – notice: 2010 by The University of Tokushima Faculty of Medicine
DBID AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
DOI 10.2152/jmi.57.95
DatabaseName CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
DatabaseTitleList MEDLINE
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Medicine
EISSN 1349-6867
EndPage 108
ExternalDocumentID 20299748
10_2152_jmi_57_95
article_jmi_57_1_2_57_1_2_95_article_char_en
Genre Research Support, Non-U.S. Gov't
Journal Article
GroupedDBID ---
.55
123
29L
2WC
3O-
53G
5GY
7.U
ADBBV
ALMA_UNASSIGNED_HOLDINGS
BAWUL
CS3
DIK
DU5
E3Z
EBS
EJD
F5P
JSF
JSH
KQ8
OK1
OVT
RJT
RNS
RZJ
TKC
TR2
X7M
XSB
ZXP
AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
ID FETCH-LOGICAL-c578t-1a644640514fcaaeafb660bd123adcddbec574c22be6b20f1274dc7b94dfedbe3
ISSN 1343-1420
IngestDate Fri Sep 17 20:48:23 EDT 2021
Tue Jul 01 01:05:53 EDT 2025
Thu Apr 24 23:07:37 EDT 2025
Wed Sep 03 06:30:02 EDT 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 1,2
Language English
LinkModel OpenURL
MergedId FETCHMERGED-LOGICAL-c578t-1a644640514fcaaeafb660bd123adcddbec574c22be6b20f1274dc7b94dfedbe3
OpenAccessLink https://www.jstage.jst.go.jp/article/jmi/57/1,2/57_1,2_95/_article/-char/en
PMID 20299748
PageCount 14
ParticipantIDs pubmed_primary_20299748
crossref_primary_10_2152_jmi_57_95
crossref_citationtrail_10_2152_jmi_57_95
jstage_primary_article_jmi_57_1_2_57_1_2_95_article_char_en
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2010-00-00
PublicationDateYYYYMMDD 2010-01-01
PublicationDate_xml – year: 2010
  text: 2010-00-00
PublicationDecade 2010
PublicationPlace Japan
PublicationPlace_xml – name: Japan
PublicationTitle The Journal of Medical Investigation
PublicationTitleAlternate J. Med. Invest.
PublicationYear 2010
Publisher The University of Tokushima Faculty of Medicine
Publisher_xml – name: The University of Tokushima Faculty of Medicine
References 9. Tenenhouse HS: Regulation of phosphorus homeostasis by the type iia na/phosphate cotransporter. Annu Rev Nutr 25: 197-214, 2005
7. Kurosu H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, Rosenblatt KP, Baum MG, Schiavi S, Hu MC, Moe OW, Kuro-o M: Regulation of fibroblast growth factor-23 signaling by klotho. J Biol Chem 281: 6120-6123, 2006
46. Segawa H, Yamanaka S, Ito M, Kuwahata M, Shono M, Yamamoto T, Miyamoto K: Internalization of renal type IIc Na-Pi cotransporter in response to a high-phosphate diet. Am J Physiol Renal Physiol 288: F587-596, 2005
29. Shimizu Y, Tada Y, Yamauchi M, Okamoto T, Suzuki H, Ito N, Fukumoto S, Sugimoto T, Fujita T: Hypophosphatemia induced by intravenous administration of saccharated ferric oxide: another form of FGF23-related hypophosphatemia. Bone 45: 814-816, 2009
30. Schouten BJ, Hunt PJ, Livesey JH, Frampton CM, Soule SG: FGF23 elevation and hypophosphatemia after intravenous iron polymaltose: a prospective study. J Clin Endocrinol Metab 94: 2332-2337, 2009
47. Wolf M: Fibroblast growth factor 23 and the future of phosphorus management. Curr Opin Nephrol Hypertens 18: 463-468, 2009
39. Segawa H, Yamanaka S, Ohno Y, Onitsuka A, Shiozawa K, Aranami F, Furutani J, Tomoe Y, Ito M, Kuwahata M, Imura A, Nabeshima Y, Miyamoto K: Correlation between hyperphosphatemia and type II Na-Pi cotransporter activity in klotho mice. Am J Physiol Renal Physiol 292: F769-779, 2007
19. Tenenhouse HS, Martel J, Gauthier C, Segawa H, Miyamoto K: Differential effects of Npt2a gene ablation and X-linked Hyp mutation on renal expression of Npt2c. Am J Physiol Renal Physiol 285: F1271-1278, 2003
32. Herak-Kramberger CM, Spindler B, Biber J, Murer H, Sabolic I: Renal type II Na/Pi-cotransporter is strongly impaired whereas the Na/sulphate-cotransporter and aquaporin 1 are unchanged in cadmium-treated rats. Pflugers Arch 432: 336-344, 1996
17. Lorenz-Depiereux B, Benet-Pages A, Eckstein G, Tenenbaum-Rakover Y, Wagenstaller J, Tiosano D, Gershoni-Baruch R, Albers N, Lichtner P, Schnabel D, Hochberg Z, Strom TM: Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. Am J Hum Genet 78: 193-201, 2006
23. Tsuchiya K: Causation of Ouch-Ouch Disease (Itai-Itai Byo)--an introductory review. I. Nature of the disease. Keio J Med 18: 181-194, 1969
36. Yusufi AN, Dousa TP: Studies on rabbit kidney brush border membranes: relationship between phosphate transport, alkaline phosphatase and NAD. Miner Electrolyte Metab 13: 397-404, 1987
4. White KE, Evans WE, O’Riordan J, Speer MC, Econs MJ, Lorenz-Depiereux B, Grabowski M, Meitinger T, TM. S: Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet 26: 345-348, 2000
33. Brzoska MM, Majewska K, Moniuszko-Jakoniuk J: Mineral status and mechanical properties of lumbar spine of female rats chronically exposed to various levels of cadmium. Bone 34: 517-526, 2004
24. Staessen JA, Roels HA, Emelianov D, Kuznetsova T, Thijs L, Vangronsveld J, Fagard R: Environmental exposure to cadmium, forearm bone density, and risk of fractures: prospective population study. Public Health and Environmental Exposure to Cadmium (PheeCad) Study Group. Lancet 353: 1140-1144, 1999
25. Alfven T, Elinder CG, Carlsson MD, Grubb A, Hellstrom L, Persson B, Pettersson C, Spang G, Schutz A, Jarup L: Low-level cadmium exposure and osteoporosis. J Bone Miner Res 15: 1579-1586, 2000
13. Miyamoto K, Ito M, Tatsumi S, Kuwahata M, Segawa H: New aspect of renal phosphate reabsorption: the type IIc sodium-dependent phosphate transporter. Am J Nephrol 27: 503-515, 2007
44. Ahn DW, Park YS: Transport of inorganic phosphate in renal cortical brush-border membrane vesicles of cadmium-intoxicated rats. Toxicol Appl Pharmacol 133: 239-243, 1995
49. Sato K, Shiraki M: Saccharated ferric oxide-induced osteomalacia in Japan: Iron-induced osteopathy due to nephropathy. Endocrine Journal 45: 431-439, 1998
1. Quarles LD: Endocrine functions of bone in mineral metabolism regulation. J Clin Invest 118: 3820-3828, 2008
8. Kuro-o M: Overview of the FGF23-Klotho axis. Pediatr Nephrol 2009
3. Razzaque MS: FGF23-mediated regulation of systemic phosphate homeostasis: is Klotho an essential player? Am J Physiol Renal Physiol 296: F470-476, 2009
6. Inoue Y, Segawa H, Kaneko I, Yamanaka S, Kusano K, Kawakami E, Furutani J, Ito M, Kuwahata M, Saito H, Fukushima N, Kato S, Kanayama HO, Miyamoto K: Role of the vitamin D receptor in FGF23 action on phosphate metabolism. Biochem J 390: 325-331, 2005
21. Adams RG, Harrison JF, Scott P: The development of cadmium-induced proteinuria, impaired renal function, and osteomalacia in alkaline battery workers. Q J Med 38: 425-443, 1969
48. Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, Fujita T, Nakahara K, Fukumoto S, Yamashita T: FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 19: 429-435, 2004
12. Segawa H, Kaneko I, Takahashi A, Kuwahata M, Ito M, Ohkido I, Tatsumi S, Miyamoto K: Growth-related renal type II Na/Pi cotransporter. J Biol Chem 277: 19665-19672, 2002
43. Robinson MK, Barfuss DW, Zalups RK: Cadmium transport and toxicity in isolated perfused segments of the renal proximal tubule. Toxicol Appl Pharmacol 121: 103-111, 1993
2. Kurosu H, Kuro-o M: The Klotho gene family as a regulator of endocrine fibroblast growth factors. Mol Cell Endocrinol 299: 72-78, 2009
26. Nogawa K, Tsuritani I, Kido T, Honda R, Yamada Y, Ishizaki M: Mechanism for bone disease found in inhabitants environmentally exposed to cadmium: decreased serum 1 alpha, 25-dihydroxyvitamin D level. Int Arch Occup Environ Health 59: 21-30, 1987
5. Shimada T, Mizutani S, Muto T, Yoneya T, Hino R, Takeda S, Takeuchi Y, Fujita T, Fukumoto S, Yamashita T: Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci USA 98: 6500-6505, 2001
22. Ishizaki A, Funkushima M: [Studies on ”Itai-itai” disease (Review)]. Nippon Eiseigaku Zasshi 23: 271-285, 1968 (in Japanese)
38. 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: Npt2a and Npt2c in mice play distinct and synergistic roles in inorganic phosphate metabolism and skeletal development. Am J Physiol Renal Physiol 297: F671-678, 2009
31. Endo I, Fukumoto S, Ozono K, Namba N, Tanaka H, Inoue D, Minagawa M, Sugimoto T, Yamauchi M, Michigami T, Matsumoto T: Clinical usefulness of measurement of fibroblast growth factor 23 (FGF23) in hypophosphatemic patients: proposal of diagnostic criteria using FGF23 measurement. Bone 42: 1235-1239, 2008
37. Segawa H, Kawakami E, Kaneko I, Kuwahata M, Ito M, Kusano K, Saito H, Fukushima N, Miyamoto K: Effect of hydrolysis-resistant FGF23-R179Q on dietary phosphate regulation of the renal type-II Na/Pi transporter. Pflugers Arch 446: 585-592, 2003
20. Kim YK, Choi JK, Kim JS, Park YS: Changes in renal function in cadmium-intoxicated rats. Pharmacol Toxicol 63: 342-350, 1988
34. Segawa H, Onitsuka A, Kuwahata M, Hanabusa E, Furutani J, Kaneko I, Tomoe Y, Aranami F, Matsumoto N, Ito M, Matsumoto M, Li M, Amizuka N, Miyamoto K: Type IIc sodium-dependent phosphate transporter regulates calcium metabolism. J Am Soc Nephrol 20: 104-113, 2009
45. Park K, Kim KR, Kim JY, Park YS: Effect of cadmium on Na-Pi cotransport kinetics in rabbit renal brush-border membrane vesicles. Toxicol Appl Pharmacol 145: 255-259, 1997
10. Biber J, Hernando N, Forster I, Murer H: Regulation of phosphate transport in proximal tubules. Pflugers Arch 458: 39-52, 2009
15. Yamamoto T, Michigami T, Aranami F, Segawa H, Yoh K, Nakajima S, Miyamoto K, Ozono K: Hereditary hypophosphatemic rickets with hypercalciuria: a study for the phosphate transporter gene type IIc and osteoblastic function. J Bone Miner Metab 25: 407-413, 2007
11. Miyamoto K, Segawa H, Ito M, Kuwahata M: Physiological regulation of renal sodium-dependent phosphate cotransporters. Jpn J Physiol 54: 93-102, 2004
18. Beck L, Karaplis AC, Amizuka N, Hewson AS, Ozawa H, Tenenhouse HS: Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities. Proc Natl Acad Sci USA 95: 5372-5377, 1998
28. Takaki A, Jimi S, Segawa M, Hisano S, Takebayashi S, Iwasaki H: Long-term cadmium exposure accelerates age-related mitochondrial changes in renal epithelial cells. Toxicology 203: 145-154, 2004
14. 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: Differential regulation of the renal sodium-phosphate cotransporters NaPi-IIa, NaPi-IIc, and PiT-2 in dietary potassium deficiency. Am J Physiol Renal Physiol 297: F350-361, 2009
27. Aoshima K, Kasuya M: Preliminary study on serum levels of 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D in cadmium-induced renal tubular dysfunction. Toxicol Lett 57: 91-99, 1991
41. Perwad F, Azam N, Zhang MY, Yamashita T, Tenenhouse HS, Portale AA: Dietary and serum phosphorus regulate fibroblast growth factor 23 expression and 1,25-dihydroxyvitamin D metabolism in mice. Endocrinology 146: 5358-5364, 2005
40. Lind Y, Engman J, Jorhem L, Glynn AW: Cadmium accumulation in liver and kidney of mice exposed to the same weekly cadmium dose continuously or once a week. Food Chem Toxicol 35: 891-895, 1997
42. Dorian C, Gattone VH, 2nd, Klaasen CD: Renal cadmium deposition and injury as a result of accumulation of cadmium-metallothionein (CdMT) by the proximal convoluted tubules--A light microscopic autoradiography study with 109CdMT. Toxicol Appl Pharmacol 114: 173-181, 1992
16. Bergwitz C, Roslin NM, Tieder M, Loredo-Osti JC, Bastepe M, Abu-Zahra H, Frappier D, Burkett K, Carpenter TO, Anderson D, Garabedian M, Sermet I, Fujiwara TM, Morgan K, Tenenhouse HS, Juppner H: SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predic
44
45
46
47
48
49
10
11
12
13
14
15
16
17
18
19
1
2
3
4
5
6
7
8
9
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
References_xml – reference: 6. Inoue Y, Segawa H, Kaneko I, Yamanaka S, Kusano K, Kawakami E, Furutani J, Ito M, Kuwahata M, Saito H, Fukushima N, Kato S, Kanayama HO, Miyamoto K: Role of the vitamin D receptor in FGF23 action on phosphate metabolism. Biochem J 390: 325-331, 2005
– reference: 7. Kurosu H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, Rosenblatt KP, Baum MG, Schiavi S, Hu MC, Moe OW, Kuro-o M: Regulation of fibroblast growth factor-23 signaling by klotho. J Biol Chem 281: 6120-6123, 2006
– reference: 14. 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: Differential regulation of the renal sodium-phosphate cotransporters NaPi-IIa, NaPi-IIc, and PiT-2 in dietary potassium deficiency. Am J Physiol Renal Physiol 297: F350-361, 2009
– reference: 8. Kuro-o M: Overview of the FGF23-Klotho axis. Pediatr Nephrol 2009
– reference: 31. Endo I, Fukumoto S, Ozono K, Namba N, Tanaka H, Inoue D, Minagawa M, Sugimoto T, Yamauchi M, Michigami T, Matsumoto T: Clinical usefulness of measurement of fibroblast growth factor 23 (FGF23) in hypophosphatemic patients: proposal of diagnostic criteria using FGF23 measurement. Bone 42: 1235-1239, 2008
– reference: 16. Bergwitz C, Roslin NM, Tieder M, Loredo-Osti JC, Bastepe M, Abu-Zahra H, Frappier D, Burkett K, Carpenter TO, Anderson D, Garabedian M, Sermet I, Fujiwara TM, Morgan K, Tenenhouse HS, Juppner H: SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis. Am J Hum Genet 78: 179-192, 2006
– reference: 12. Segawa H, Kaneko I, Takahashi A, Kuwahata M, Ito M, Ohkido I, Tatsumi S, Miyamoto K: Growth-related renal type II Na/Pi cotransporter. J Biol Chem 277: 19665-19672, 2002
– reference: 22. Ishizaki A, Funkushima M: [Studies on ”Itai-itai” disease (Review)]. Nippon Eiseigaku Zasshi 23: 271-285, 1968 (in Japanese)
– reference: 17. Lorenz-Depiereux B, Benet-Pages A, Eckstein G, Tenenbaum-Rakover Y, Wagenstaller J, Tiosano D, Gershoni-Baruch R, Albers N, Lichtner P, Schnabel D, Hochberg Z, Strom TM: Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. Am J Hum Genet 78: 193-201, 2006
– reference: 29. Shimizu Y, Tada Y, Yamauchi M, Okamoto T, Suzuki H, Ito N, Fukumoto S, Sugimoto T, Fujita T: Hypophosphatemia induced by intravenous administration of saccharated ferric oxide: another form of FGF23-related hypophosphatemia. Bone 45: 814-816, 2009
– reference: 45. Park K, Kim KR, Kim JY, Park YS: Effect of cadmium on Na-Pi cotransport kinetics in rabbit renal brush-border membrane vesicles. Toxicol Appl Pharmacol 145: 255-259, 1997
– reference: 13. Miyamoto K, Ito M, Tatsumi S, Kuwahata M, Segawa H: New aspect of renal phosphate reabsorption: the type IIc sodium-dependent phosphate transporter. Am J Nephrol 27: 503-515, 2007
– reference: 25. Alfven T, Elinder CG, Carlsson MD, Grubb A, Hellstrom L, Persson B, Pettersson C, Spang G, Schutz A, Jarup L: Low-level cadmium exposure and osteoporosis. J Bone Miner Res 15: 1579-1586, 2000
– reference: 46. Segawa H, Yamanaka S, Ito M, Kuwahata M, Shono M, Yamamoto T, Miyamoto K: Internalization of renal type IIc Na-Pi cotransporter in response to a high-phosphate diet. Am J Physiol Renal Physiol 288: F587-596, 2005
– reference: 21. Adams RG, Harrison JF, Scott P: The development of cadmium-induced proteinuria, impaired renal function, and osteomalacia in alkaline battery workers. Q J Med 38: 425-443, 1969
– reference: 10. Biber J, Hernando N, Forster I, Murer H: Regulation of phosphate transport in proximal tubules. Pflugers Arch 458: 39-52, 2009
– reference: 37. Segawa H, Kawakami E, Kaneko I, Kuwahata M, Ito M, Kusano K, Saito H, Fukushima N, Miyamoto K: Effect of hydrolysis-resistant FGF23-R179Q on dietary phosphate regulation of the renal type-II Na/Pi transporter. Pflugers Arch 446: 585-592, 2003
– reference: 30. Schouten BJ, Hunt PJ, Livesey JH, Frampton CM, Soule SG: FGF23 elevation and hypophosphatemia after intravenous iron polymaltose: a prospective study. J Clin Endocrinol Metab 94: 2332-2337, 2009
– reference: 15. Yamamoto T, Michigami T, Aranami F, Segawa H, Yoh K, Nakajima S, Miyamoto K, Ozono K: Hereditary hypophosphatemic rickets with hypercalciuria: a study for the phosphate transporter gene type IIc and osteoblastic function. J Bone Miner Metab 25: 407-413, 2007
– reference: 20. Kim YK, Choi JK, Kim JS, Park YS: Changes in renal function in cadmium-intoxicated rats. Pharmacol Toxicol 63: 342-350, 1988
– reference: 5. Shimada T, Mizutani S, Muto T, Yoneya T, Hino R, Takeda S, Takeuchi Y, Fujita T, Fukumoto S, Yamashita T: Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci USA 98: 6500-6505, 2001
– reference: 26. Nogawa K, Tsuritani I, Kido T, Honda R, Yamada Y, Ishizaki M: Mechanism for bone disease found in inhabitants environmentally exposed to cadmium: decreased serum 1 alpha, 25-dihydroxyvitamin D level. Int Arch Occup Environ Health 59: 21-30, 1987
– reference: 40. Lind Y, Engman J, Jorhem L, Glynn AW: Cadmium accumulation in liver and kidney of mice exposed to the same weekly cadmium dose continuously or once a week. Food Chem Toxicol 35: 891-895, 1997
– reference: 2. Kurosu H, Kuro-o M: The Klotho gene family as a regulator of endocrine fibroblast growth factors. Mol Cell Endocrinol 299: 72-78, 2009
– reference: 38. 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: Npt2a and Npt2c in mice play distinct and synergistic roles in inorganic phosphate metabolism and skeletal development. Am J Physiol Renal Physiol 297: F671-678, 2009
– reference: 4. White KE, Evans WE, O’Riordan J, Speer MC, Econs MJ, Lorenz-Depiereux B, Grabowski M, Meitinger T, TM. S: Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet 26: 345-348, 2000
– reference: 1. Quarles LD: Endocrine functions of bone in mineral metabolism regulation. J Clin Invest 118: 3820-3828, 2008
– reference: 34. Segawa H, Onitsuka A, Kuwahata M, Hanabusa E, Furutani J, Kaneko I, Tomoe Y, Aranami F, Matsumoto N, Ito M, Matsumoto M, Li M, Amizuka N, Miyamoto K: Type IIc sodium-dependent phosphate transporter regulates calcium metabolism. J Am Soc Nephrol 20: 104-113, 2009
– reference: 35. Selvaraj P, Prabhu Anand S, Harishankar M, Alagarasu K: Plasma 1,25 dihydroxy vitamin D3 level and expression of vitamin d receptor and cathelicidin in pulmonary tuberculosis. J Clin Immunol 29: 470-478, 2009
– reference: 23. Tsuchiya K: Causation of Ouch-Ouch Disease (Itai-Itai Byo)--an introductory review. I. Nature of the disease. Keio J Med 18: 181-194, 1969
– reference: 18. Beck L, Karaplis AC, Amizuka N, Hewson AS, Ozawa H, Tenenhouse HS: Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities. Proc Natl Acad Sci USA 95: 5372-5377, 1998
– reference: 32. Herak-Kramberger CM, Spindler B, Biber J, Murer H, Sabolic I: Renal type II Na/Pi-cotransporter is strongly impaired whereas the Na/sulphate-cotransporter and aquaporin 1 are unchanged in cadmium-treated rats. Pflugers Arch 432: 336-344, 1996
– reference: 33. Brzoska MM, Majewska K, Moniuszko-Jakoniuk J: Mineral status and mechanical properties of lumbar spine of female rats chronically exposed to various levels of cadmium. Bone 34: 517-526, 2004
– reference: 36. Yusufi AN, Dousa TP: Studies on rabbit kidney brush border membranes: relationship between phosphate transport, alkaline phosphatase and NAD. Miner Electrolyte Metab 13: 397-404, 1987
– reference: 49. Sato K, Shiraki M: Saccharated ferric oxide-induced osteomalacia in Japan: Iron-induced osteopathy due to nephropathy. Endocrine Journal 45: 431-439, 1998
– reference: 11. Miyamoto K, Segawa H, Ito M, Kuwahata M: Physiological regulation of renal sodium-dependent phosphate cotransporters. Jpn J Physiol 54: 93-102, 2004
– reference: 28. Takaki A, Jimi S, Segawa M, Hisano S, Takebayashi S, Iwasaki H: Long-term cadmium exposure accelerates age-related mitochondrial changes in renal epithelial cells. Toxicology 203: 145-154, 2004
– reference: 19. Tenenhouse HS, Martel J, Gauthier C, Segawa H, Miyamoto K: Differential effects of Npt2a gene ablation and X-linked Hyp mutation on renal expression of Npt2c. Am J Physiol Renal Physiol 285: F1271-1278, 2003
– reference: 24. Staessen JA, Roels HA, Emelianov D, Kuznetsova T, Thijs L, Vangronsveld J, Fagard R: Environmental exposure to cadmium, forearm bone density, and risk of fractures: prospective population study. Public Health and Environmental Exposure to Cadmium (PheeCad) Study Group. Lancet 353: 1140-1144, 1999
– reference: 3. Razzaque MS: FGF23-mediated regulation of systemic phosphate homeostasis: is Klotho an essential player? Am J Physiol Renal Physiol 296: F470-476, 2009
– reference: 39. Segawa H, Yamanaka S, Ohno Y, Onitsuka A, Shiozawa K, Aranami F, Furutani J, Tomoe Y, Ito M, Kuwahata M, Imura A, Nabeshima Y, Miyamoto K: Correlation between hyperphosphatemia and type II Na-Pi cotransporter activity in klotho mice. Am J Physiol Renal Physiol 292: F769-779, 2007
– reference: 47. Wolf M: Fibroblast growth factor 23 and the future of phosphorus management. Curr Opin Nephrol Hypertens 18: 463-468, 2009
– reference: 43. Robinson MK, Barfuss DW, Zalups RK: Cadmium transport and toxicity in isolated perfused segments of the renal proximal tubule. Toxicol Appl Pharmacol 121: 103-111, 1993
– reference: 42. Dorian C, Gattone VH, 2nd, Klaasen CD: Renal cadmium deposition and injury as a result of accumulation of cadmium-metallothionein (CdMT) by the proximal convoluted tubules--A light microscopic autoradiography study with 109CdMT. Toxicol Appl Pharmacol 114: 173-181, 1992
– reference: 44. Ahn DW, Park YS: Transport of inorganic phosphate in renal cortical brush-border membrane vesicles of cadmium-intoxicated rats. Toxicol Appl Pharmacol 133: 239-243, 1995
– reference: 48. Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, Fujita T, Nakahara K, Fukumoto S, Yamashita T: FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 19: 429-435, 2004
– reference: 41. Perwad F, Azam N, Zhang MY, Yamashita T, Tenenhouse HS, Portale AA: Dietary and serum phosphorus regulate fibroblast growth factor 23 expression and 1,25-dihydroxyvitamin D metabolism in mice. Endocrinology 146: 5358-5364, 2005
– reference: 9. Tenenhouse HS: Regulation of phosphorus homeostasis by the type iia na/phosphate cotransporter. Annu Rev Nutr 25: 197-214, 2005
– reference: 27. Aoshima K, Kasuya M: Preliminary study on serum levels of 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D in cadmium-induced renal tubular dysfunction. Toxicol Lett 57: 91-99, 1991
– ident: 9
  doi: 10.1146/annurev.nutr.25.050304.092642
– ident: 7
  doi: 10.1074/jbc.C500457200
– ident: 41
  doi: 10.1210/en.2005-0777
– ident: 10
  doi: 10.1007/s00424-008-0580-8
– ident: 42
  doi: 10.1016/0041-008X(92)90066-2
– ident: 43
  doi: 10.1006/taap.1993.1134
– ident: 5
  doi: 10.1073/pnas.101545198
– ident: 1
  doi: 10.1172/JCI36479
– ident: 22
– ident: 38
  doi: 10.1152/ajprenal.00156.2009
– ident: 25
  doi: 10.1359/jbmr.2000.15.8.1579
– ident: 28
  doi: 10.1016/j.tox.2004.06.005
– ident: 12
  doi: 10.1074/jbc.M200943200
– ident: 4
  doi: 10.1038/81664
– ident: 6
  doi: 10.1042/BJ20041799
– ident: 37
  doi: 10.1007/s00424-003-1084-1
– ident: 8
  doi: 10.1007/s00467-009-1260-4
– ident: 15
  doi: 10.1007/s00774-007-0776-6
– ident: 18
  doi: 10.1073/pnas.95.9.5372
– ident: 35
  doi: 10.1007/s10875-009-9277-9
– ident: 45
  doi: 10.1006/taap.1997.8180
– ident: 48
  doi: 10.1359/JBMR.0301264
– ident: 11
  doi: 10.2170/jjphysiol.54.93
– ident: 31
  doi: 10.1016/j.bone.2008.02.014
– ident: 49
  doi: 10.1507/endocrj.45.431
– ident: 17
  doi: 10.1086/499410
– ident: 14
  doi: 10.1152/ajprenal.90765.2008
– ident: 34
  doi: 10.1681/ASN.2008020177
– ident: 44
  doi: 10.1006/taap.1995.1147
– ident: 20
  doi: 10.1111/j.1600-0773.1988.tb00966.x
– ident: 33
  doi: 10.1016/j.bone.2003.12.002
– ident: 23
  doi: 10.2302/kjm.18.181
– ident: 40
  doi: 10.1016/S0278-6915(97)00068-9
– ident: 3
  doi: 10.1152/ajprenal.90538.2008
– ident: 46
  doi: 10.1152/ajprenal.00097.2004
– ident: 32
  doi: 10.1007/s004240050141
– ident: 24
  doi: 10.1016/S0140-6736(98)09356-8
– ident: 19
  doi: 10.1152/ajprenal.00252.2003
– ident: 30
  doi: 10.1210/jc.2008-2396
– ident: 36
– ident: 27
  doi: 10.1016/0378-4274(91)90123-N
– ident: 39
  doi: 10.1152/ajprenal.00248.2006
– ident: 29
  doi: 10.1016/j.bone.2009.06.017
– ident: 13
  doi: 10.1159/000107069
– ident: 16
  doi: 10.1086/499409
– ident: 47
  doi: 10.1097/MNH.0b013e328331a8c8
– ident: 2
  doi: 10.1016/j.mce.2008.10.052
– ident: 21
– ident: 26
  doi: 10.1007/BF00377675
SSID ssj0033555
Score 1.8959973
Snippet Phosphaturia has been documented following cadmium (Cd) exposure in both humans and experimental animals. The fibroblast growth factor 23 (FGF23)/klotho axis...
SourceID pubmed
crossref
jstage
SourceType Index Database
Enrichment Source
Publisher
StartPage 95
SubjectTerms Animals
cadmium
Cadmium - toxicity
Extracellular Matrix Proteins - genetics
Female
FGF23
Fibroblast Growth Factors - genetics
Fibroblast Growth Factors - physiology
Hypophosphatemia, Familial - chemically induced
Mice
Mice, Inbred C57BL
Mice, Knockout
PHEX Phosphate Regulating Neutral Endopeptidase - genetics
phosphate
proximal tubule
RNA, Messenger - analysis
Sodium-Phosphate Cotransporter Proteins, Type IIa - analysis
Sodium-Phosphate Cotransporter Proteins, Type IIa - physiology
transporter
Title Fibroblast growth factor 23 mediates the phosphaturic actions of cadmium
URI https://www.jstage.jst.go.jp/article/jmi/57/1,2/57_1,2_95/_article/-char/en
https://www.ncbi.nlm.nih.gov/pubmed/20299748
Volume 57
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
ispartofPNX The Journal of Medical Investigation, 2010, Vol.57(1,2), pp.95-108
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3Nb9MwFLfKQIgL4pvyJQtxQKpSEseJE3GagKps2sRhk3aL_JW1hTRTSVTBX89z7LgZ22FwSSvHdhS_5_fhvPd7CL0jqc4iKniQlpQGtIziIFOwr0KlQJnrLJRlFyB7nM5P6cFZcjYabYfZJY2Yyt_X5pX8D1WhDehqsmT_gbJ-UmiA_0BfuAKF4XojGs_A160F2L_N5Bzc6WbhyudMSGxTQsyhapcLtah_XiwMhqeBZ5U--k1yVS0dGMNqxzcDOInKfchZ7vA4dh_u90HR8aqLB5i1FcgGf16jz_m2M0vny0393bfP2k3b2CpSk4N2_cvrhMN2yw10dHcYu6hXy-FphItItaIzNmCnlNgm3bflQZrZghu9vLWA1D1fwbxkIEBtxU2niqMO8uGKlDeleI2Ur5bThE37EUMk7b80nI87BI_HDC5gaJGwIk9uoduEscjEgn7-etir8BiMsKTz1N0rWUgqM_SDf-olQ-bOCmx5A9JwyTfpbJSTB-i-cy7wvuWUh2ik14_Q3SMXPvEYzXcMgy3DYMswmMS4ZxgMDIOHDIMdw-C6xI5hnqDT2ZeTT_PAldIIJIjkJog42L0pNWD3peRc81KkaSgU2C1cSaVgJyeMSkKETgUJy4gwqiQTOVWlhrvxU7S3rtf6OcKKs1BnWRzyLKdcCp4yMKNhUq4inct4jN7361JIhzNvyp38KK6s_hi99V0vLLjKdZ0-2sX1Xdx-67tEBel_8sTfNEmLICPG6JmliB9NQrDAGM1e3OThL9E9Gy5iztxeob1m0-rXYIU24k3HMXA9_nb0B2c8j74
linkProvider Flying Publisher
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Fibroblast+growth+factor+23+mediates+the+phosphaturic+actions+of+cadmium&rft.jtitle=The+journal+of+medical+investigation&rft.au=Aranami%2C+Fumito&rft.au=Segawa%2C+Hiroko&rft.au=Furutani%2C+Junya&rft.au=Kuwahara%2C+Shoji&rft.date=2010&rft.issn=1343-1420&rft.eissn=1349-6867&rft.volume=57&rft.issue=1%2C2&rft.spage=95&rft.epage=108&rft_id=info:doi/10.2152%2Fjmi.57.95&rft.externalDBID=n%2Fa&rft.externalDocID=10_2152_jmi_57_95
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1343-1420&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1343-1420&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1343-1420&client=summon