Growth hormone and Klotho

Journal of Endocrinology

Volumn 219, Issue 2, 2013, Pages

  Schmid, Christoph ^a   Neidert, Marian C ^a   Tschopp, Oliver ^a   Sze, Lisa ^a,b   Bernays, René L ^a,c  

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^b Division of Endocrinology and Diabetes   (Switzerland)

^c KLINIK HIRSLANDEN   (Switzerland)

Author keywords

Acromegaly; FGF23; Growth hormone; IGF1; Klotho

Indexed keywords

BETA GLUCURONIDASE; CELL SURFACE RECEPTOR; CREATININE; FIBROBLAST GROWTH FACTOR 19; FIBROBLAST GROWTH FACTOR 23; FIBROBLAST GROWTH FACTOR RECEPTOR 1; GLUCOSE; GROWTH HORMONE; INSULIN RECEPTOR; KLOTHO PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE 1; PARATHYROID HORMONE; PHOSPHATE; SOMATOMEDIN; SOMATOMEDIN BINDING PROTEIN; SOMATOMEDIN C;

ACROMEGALY; AMINO ACID SEQUENCE; AUTOPHOSPHORYLATION; AUTOSOMAL DOMINANT HYPOPHOSPHATEMIC RICKETS; BILE ACID SYNTHESIS; BINDING SITE; BODY TEMPERATURE; CAENORHABDITIS ELEGANS; CEREBROSPINAL FLUID; CLINICAL FEATURE; CONFORMATIONAL TRANSITION; DISEASE ACTIVITY; ENERGY EXPENDITURE; ENZYME LINKED IMMUNOSORBENT ASSAY; EOSINOPHIL; EXTRACELLULAR FLUID; EXTRACELLULAR SPACE; FACIES; GENE MUTATION; GIGANTISM; GLOMERULUS FILTRATION RATE; GROWTH; GROWTH HORMONE DEFICIENCY; GROWTH HORMONE RELEASE; GROWTH HORMONE SECRETING CELL; HALF LIFE TIME; HEART LEFT VENTRICLE HYPERTROPHY; HUMAN; HYPERPARATHYROIDISM; HYPERPHOSPHATEMIA; HYPOPHOSPHATEMIA; HYPOPHYSIS ADENOMA; HYPOPHYSIS FUNCTION; HYPOPITUITARISM; INSULIN LIKE ACTIVITY; KIDNEY DISTAL TUBULE; LIFESPAN; MITOGENESIS; MOLECULAR WEIGHT; MORTALITY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OXIDATIVE STRESS; PHOSPHATE EXCRETION; PHOSPHATE INTAKE; PHOSPHATE TRANSPORT; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; VITAMIN D METABOLISM; WHITE ADIPOSE TISSUE; ZEBRA FISH;

ACROMEGALY; FGF23; GROWTH HORMONE; IGF1; KLOTHO;

ACROMEGALY; ANIMALS; CALCIUM; DISEASE MODELS, ANIMAL; GLUCURONIDASE; GROWTH HORMONE; HUMANS; MICE; SIGNAL TRANSDUCTION;

EID: 84885717394     PISSN: 00220795     EISSN: 14796805     Source Type: Journal    
DOI: 10.1530/JOE-13-0285     Document Type: Review

References (178)

1. Abramovitz L, Rubinek T, Ligumsky H, Bose S, Barshack I, Avivi C, Kaufman B & Wolf I 2011 KL1 internal repeat mediates Klotho tumor suppressor activities and inhibits bFGF and IGF-I signaling in pancreatic cancer. Clinical Cancer Research 17 4254-4266. (doi:10.1158/ 1078-0432.CCR-10-2749)
2. ADHR Consortium 2000 Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nature Genetics 26 345-348. (doi:10.1038/81664)
3. Akimoto T, Yoshizawa H, Watanabe Y, Numata A, Yamazaki T, Takeshima E, Iwazu K, Komada T, Otani N, Morishita Y et al. 2012 Characteristics of urinary and serum soluble Klotho protein in patients with different degrees of chronic kidney disease. BMC Nephrology 13 155. (doi:10.1186/1471-2369-13-155)
4. Akimoto T, Kimura T,Watanabe Y, Ishikawa N, Iwazu Y, Saito O, Muto S, Yagisawa T & Kusano E 2013 The impact of nephrectomy and renal transplantation on serumlevels of soluble Klotho protein. Transplantation Proceedings 45 134-136. (doi:10.1016/j.transproceed.2012.07.150)
5. Alexander RT, Woudenberg-Vrenken TE, Buurman J, Dijkman H, van der Eerden BC, van Leeuwen JP, Bindels RJ & Hoenderop JG 2009 Klotho prevents renal calcium loss. Journal of the American Society of Nephrology 20 2371-2379. (doi:10.1681/ASN.2008121273)
6. Amitani M, Asakawa A, Amitani H, Kaimoto K, Sameshima N, Koyama KI, Haruta I, Tsai M, Nakahara T, UshikaiMet al. 2013 Plasma klotho levels decrease in both anorexia nervosa and obesity. Nutrition 29 1106-1109. (doi:10.1016/j.nut.2013.02.005)
7. Andrukhova O, Zeitz U, Goetz R, Mohammadi M, Lanske B & Erben RG 2012 FGF23 acts directly on renal proximal tubules to induce phosphaturia through activation of the ERK1/2-SGK1 signaling pathway. Bone 51 621-628. (doi:10.1016/j.bone.2012.05.015)
8. Arking DE, Krebsova A, Macek MSr,MacekMJr, Arking A, Mian IS, Fried L, Hamosh A, Dey S, McIntosh I et al. 2002 Association of human aging with a functional variant of Klotho. PNAS 99 856-861. (doi:10.1073/ pnas.022484299)
9. Asai O, Nakatani K, Tanaka T, Sakan H, Imura A, Yoshimoto S, Samejima K, Yamaguchi Y, Matsui M, Akai Y et al. 2012 Decreased renal α-Klotho expression in early diabetic nephropathy in humans and mice and its possible role in urinary calcium excretion. Kidney International 81 539-547. (doi:10.1038/ki.2011.423)
10. Bai X, Miao D, Li J, Goltzman D & Karaplis AC 2004 Transgenic mice overexpressing human fibroblast growth factor 23 (R176Q) delineate a putative role for parathyroid hormone in renal phosphate wasting disorders. Endocrinology 145 5269-5279. (doi:10.1210/en.2004-0233)
11. Bauer C, Brucker R, Butzberger S & Schmid C 2010 Hypophosphataemiainducing mesenchymal tumour in the foot. BMJ Case Reports. (doi:10.1136/bcr.06.2009.2034)
12. Ben-Dov IZ, Galitzer H, Lavi-Moshayoff V, Goetz R, Kuro-o M, Mohammadi M, Sirkis R, Naveh-Many T & Silver J 2007 The parathyroid is a target organ for FGF23 in rats. Journal of Clinical Investigation 117 4003-4008. (doi:10.1172/JCI32409)
13. Berryman DE, Christiansen JS, Johannsson G, Thorner MO & Kopchick JJ 2008 Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models. Growth Hormone & IGF Research 18 455-471. (doi:10.1016/j.ghir.2008.05.005)
14. Bianda T, Hussain MA, Glatz Y, Bouillon R, Froesch ER & Schmid C 1997 Effects of short-term insulin-like growth factor-I or growth hormone treatment on bone turnover, renal phosphate reabsorption and 1,25 dihydroxyvitamin D3 production in healthy man. Journal of Internal Medicine 241 143-150. (doi:10.1046/j.1365-2796.0997.94101000.x)
15. Bianda T, Glatz Y, Bouillon R, Froesch ER & Schmid C 1998 Effects of short-term insulin-like growth factor-I (IGF-I) or growth hormone (GH) treatment on bone metabolism and on production of 1,25-dihydroxycholecalciferol in GH-deficient adults. Journal of Clinical Endocrinology and Metabolism 83 81-87. (doi:10.1210/jc.83.1.81)
16. Bloch L, Sineshchekova O, Reichenbach D, Reiss K, Saftig P, Kuro-o M & Kaether C 2009 Klotho is a substrate for aα-, β-and γ-secretase. FEBS Letters 583 3221-3224. (doi:10.1016/j.febslet.2009.09.009)
17. Boger RH, Skamira C, Bode-Boger SM, Brabant G, von zur Muhlen A & Frolich JC 1996 Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency. A double-blind, placebo-controlled study. Journal of Clinical Investigation 98 2706-2713. (doi:10.1172/JCI109095)
18. Brownstein CA, Adler F, Nelson-Williams C, Iijima J, Li P, Imura A, Nabeshima Y, Reyes-Mugica M, Carpenter TO & Lifton RP 2008 A translocation causing increased α-Klotho level results in hypophosphatemic rickets and hyperparathyroidism. PNAS 105 3455-3460. (doi:10.1073/pnas.0712361105)
19. Carracedo J, Buendia P, Merino A, Madueno JA, Peralbo E, Ortiz A, Martin-Malo A, Aljama P, Rodriguez M & Ramirez R 2012 Klotho modulates the stress response in human senescent endothelial cells. Mechanisms of Ageing and Development 133 647-654. (doi:10.1016/ j.mad.2012.09.002)
20. Cha SK, Ortega B, Kurosu H, Rosenblatt KP, Kuro OM & Huang CL 2008 Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1. PNAS 105 9805-9810. (doi:10.1073/pnas.0803223105)
21. Chang Q, Hoefs S, van der Kemp AW, Topala CN, Bindels RJ & Hoenderop JG 2005 The β-glucuronidase Klotho hydrolyzes and activates the TRPV5 channel. Science 310 490-493. (doi:10.1126/science.1114245)
22. Chen CD, Podvin S, Gillespie E, Leeman SE & Abraham CR 2007 Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17. PNAS 104 19796-09801. (doi:10.1073/pnas.0709805104)
23. Chen B, Wang X, Zhao W & Wu J 2010 Klotho inhibits growth and promotes apoptosis in human lung cancer cell line A549. Journal of Experimental & Clinical Cancer Research 29 99. (doi:10.1186/ 1756-9966-29-99)
24. Chen B, Ma X, Liu S, Zhao W & Wu J 2012 Inhibition of lung cancer cells growth, motility and induction of apoptosis by Klotho, a novel secreted Wnt antagonist, in a dose-dependentmanner. Cancer Biology & Therapy 13 1221-1228. (doi:10.4161/cbt.21420)
25. Chen CD, Sloane JA, Li H, Aytan N, Giannaris EL, Zeldich E, Hinman JD, Dedeoglu A, Rosene DL, Bansal R et al. 2013a The antiaging protein Klotho enhances oligodendrocyte maturation and myelination of the CNS. Journal of Neuroscience 33 1927-0939. (doi:10.1523/JNEUROSCI. 2080-12.2013)
26. Chen TH, Kuro OM, Chen CH, Sue YM, Chen YC, Wu HH & Cheng CY 2013b The secreted Klotho protein restores phosphate retention and suppresses accelerated aging in Klotho mutantmice. European Journal of Pharmacology 698 67-73. (doi:10.1016/j.ejphar.2012.09.032)
27. Chihara Y, Rakugi H, Ishikawa K, Ikushima M, Maekawa Y, Ohta J, Kida I & Ogihara T 2006 Klotho protein promotes adipocyte differentiation. Endocrinology 147 3835-3842. (doi:10.1210/en.2005-1529)
28. Clemmons DR 2011 Consensus statement on the standardization and evaluation of growth hormone and insulin-like growth factor assays. Clinical Chemistry 57 555-559. (doi:10.1373/clinchem.2010.150631)
29. Corvilain J, Abramow M & Bergans A 1962 Some effects of human growth hormone on renal hemodynamics and on tubular phosphate transport in man. Journal of Clinical Investigation 41 1230-1235. (doi:10.1172/ JCI104584)
30. Crasto CL, Semba RD, Sun K, Cappola AR, Bandinelli S & Ferrucci L 2012 Relationship of low-circulating "anti-aging" Klotho hormone with disability in activities of daily living among older community-dwelling adults. Rejuvenation Research 15 295-301. (doi:10.1089/rej.2011.1268)
31. Daughaday WH, Hall K, Raben MS, Salmon WD Jr, van den Brande JL & van Wyk JJ 1972 Somatomedin: proposed designation for sulphation factor. Nature 235 107. (doi:10.1038/235107a0)
32. Deary IJ, Harris SE, Fox HC, Hayward C, Wright AF, Starr JM & Whalley LJ 2005 KLOTHO genotype and cognitive ability in childhood and old age in the same individuals. Neuroscience Letters 378 22-27. (doi:10.1016/ j.neulet.2004.12.005)
33. Devaraj S, Syed B, Chien A & Jialal I 2012 Validation of an immunoassay for soluble Klotho protein: decreased levels in diabetes and increased levels in chronic kidney disease. American Journal of Clinical Pathology 137 479-485. (doi:10.1309/AJCPGPMAF7SFRBO4)
34. Dhingra R, Sullivan LM, Fox CS,Wang TJ, D'Agostino RB Sr, Gaziano JM & Vasan RS 2007 Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Archives of Internal Medicine 167 879-885. (doi:10.1001/archinte.167.9.879)
35. Di Marco GS, Konig M, Stock C, Wiesinger A, Hillebrand U, Reiermann S, Reuter S, Amler S, Kohler G, Buck F et al. 2013 High phosphate directly affects endothelial function by downregulating annexin II. Kidney International 83 213-222. (doi:10.1038/ki.2012.300)
36. Doi S, Zou Y, Togao O, Pastor JV, John GB, Wang L, Shiizaki K, Gotschall R, Schiavi S, Yorioka N et al. 2011 Klotho inhibits transforming growth factor-β1 (TGF-β1) signaling and suppresses renal fibrosis and cancer metastasis in mice. Journal of Biological Chemistry 286 8655-8665. (doi:10.1074/jbc.M110.174037)
37. Dulak NC & Temin HM 1973 A partially purified polypeptide fraction from rat liver cell conditioned medium with multiplication-stimulating activity for embryo fibroblasts. Journal of Cellular Physiology 81 153-160. (doi:10.1002/jcp.1040810204)
38. Ellam TJ & Chico TJ 2012 Phosphate: the new cholesterol? The role of the phosphate axis in non-uremic vascular disease Atherosclerosis 220 310-318. (doi:10.1016/j.atherosclerosis.2011.09.002)
39. Evans LM, Davies JS, Anderson RA, Ellis GR, Jackson SK, Lewis MJ, Frenneaux MP, Rees A& ScanlonMF 2000 The effect of GH replacement therapy on endothelial function and oxidative stress in adult growth hormone deficiency. European Journal of Endocrinology 142 254-262. (doi:10.1530/eje.0.1420254)
40. Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, Isakova T, Gutierrez OM, Aguillon-Prada R, Lincoln J, Hare JM et al. 2011 FGF23 induces left ventricular hypertrophy. Journal of Clinical Investigation 121 4393-4408. (doi:10.1172/JCI46122)
41. Foley RN 2009 Phosphate levels and cardiovascular disease in the general population. Clinical Journal of the American Society of Nephrology 4 1136-1139. (doi:10.2215/CJN.01660309)
42. Froesch ER, Buergi H, Ramseier EB, Bally P & Labhart A 1963 Antibodysuppressible and nonsuppressible insulin-like activities in human serum and their physiologic significance. an insulin assay with adipose tissue of increased precision and specificity. Journal of Clinical Investigation 42 1816-1834. (doi:10.1172/JCI104866)
43. Galitzer H, Ben-Dov IZ, Silver J & Naveh-Many T 2010 Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease. Kidney International 77 211-218. (doi:10.1038/ki.2009.464)
44. Gattineni J, Bates C, Twombley K, Dwarakanath V, Robinson ML, Goetz R, Mohammadi M & Baum M 2009 FGF23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1. American Journal of Physiology. Renal Physiology 297 F282-F291. (doi:10.1152/ajprenal.90742.2008)
45. German DC, Khobahy I, Pastor J, Kuro OM & Liu X 2012 Nuclear localization of Klotho in brain: an anti-aging protein. Neurobiology of Aging 33 e1425-e1430. (doi:10.1016/j.neurobiolaging.2011.12.018)
46. Giustina A, Chanson P, Bronstein MD, Klibanski A, Lamberts S, Casanueva FF, Trainer P, Ghigo E, Ho K & Melmed S 2010 A consensus on criteria for cure of acromegaly. Journal of Clinical Endocrinology and Metabolism 95 3141-3148. (doi:10.1210/jc.2009-2670)
47. Godowski PJ, Leung DW, Meacham LR, Galgani JP, Hellmiss R, Keret R, Rotwein PS, Parks JS, Laron Z & Wood WI 1989 Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron-type dwarfism. PNAS 86 8083-8087. (doi:10.1073/pnas.86.20.8083)
48. Guler HP, Zapf J, Schmid C & Froesch ER 1989 Insulin-like growth factors I and II in healthy man. Estimations of half-lives and production rates. Acta Endocrinologica 121 753-758. (doi:10.1530/acta.0.1210753)
49. Hesse M, Frohlich LF, Zeitz U, Lanske B & Erben RG 2007 Ablation of vitamin D signaling rescues bone, mineral, and glucose homeostasis in Fgf-23 deficient mice. Matrix Biology 26 75-84. (doi:10.1016/j.matbio. 2006.10.003)
50. Hu MC, Shi M, Zhang J, Pastor J, Nakatani T, Lanske B, Razzaque MS, Rosenblatt KP, Baum MG, Kuro-o M et al. 2010 Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule. FASEB Journal 24 3438-3450. (doi:10.1096/ fj.10-154765)
51. Hu MC, ShiM, Zhang J, Quinones H, Griffith C, Kuro-o M& Moe OW 2011 Klotho deficiency causes vascular calcification in chronic kidney disease. Journal of the American Society of Nephrology 22 124-136. (doi:10.1681/ASN.2009121311)
52. Hu MC, Shiizaki K, Kuro-o M & Moe OW 2013 Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism. Annual Review of Physiology 75 503-533. (doi:10.1146/annurev-physiol-030212-183727)
53. Huang CL 2012 Regulation of ion channels by secreted Klotho. Advances in Experimental Medicine and Biology 728 100-106. (doi:10.1007/978-1-4614-0887-1_7)
54. Ichikawa S, Imel EA, Kreiter ML, Yu X, Mackenzie DS, Sorenson AH, Goetz R, Mohammadi M, White KE & Econs MJ 2007 A homozygous missense mutation in human KLOTHOcauses severe tumoral calcinosis. Journal of Clinical Investigation 117 2684-2691. (doi:10.1172/JCI31330)
55. Ikkos D, Ljunggren H & Luft R 1956 Glomerular filtration rate and renal plasma flow in acromegaly. Acta Endocrinologica 21 226-236. (doi:10.1530/acta.0.0210226)
56. Ikushima M, Rakugi H, Ishikawa K, Maekawa Y, Yamamoto K, Ohta J, Chihara Y, Kida I & Ogihara T 2006 Anti-apoptotic and anti-senescence effects of Klotho on vascular endothelial cells. Biochemical and Biophysical Research Communications 339 827-832. (doi:10.1016/j.bbrc. 2005.11.094)
57. Imura A, Iwano A, Tohyama O, Tsuji Y, Nozaki K, Hashimoto N, Fujimori T & Nabeshima Y 2004 Secreted Klotho protein in sera and CSF: implication for post-translational cleavage in release of Klotho protein from cell membrane. FEBS Letters 565 143-147. (doi:10.1016/j.febslet. 2004.03.090)
58. Imura A, Tsuji Y, Murata M, Maeda R, Kubota K, Iwano A, Obuse C, Togashi K, Tominaga M, Kita N et al. 2007 α-Klotho as a regulator of calcium homeostasis. Science 316 1615-1618. (doi:10.1126/ science.1135901)
59. Ito S, Kinoshita S, Shiraishi N, Nakagawa S, Sekine S, Fujimori T & Nabeshima YI 2000 Molecular cloning and expression analyses of mouse bKlotho, which encodes a novel Klotho family protein. Mechanisms of Development 98 115-109. (doi:10.1016/S0925-4773(00) 00439-1)
60. Ito S, Fujimori T, Hayashizaki Y & Nabeshima Y 2002 Identification of a novel mouse membrane-bound family 1 glycosidase-like protein, which carries an atypical active site structure. Biochimica et Biophysica Acta 1576 341-345. (doi:10.1016/S0167-4781(02)00281-6)
61. Ito N, Fukumoto S, Taguchi M, Takeshita A, Takeuchi Y, Yamada S & Fujita T 2007 Fibroblast growth factor (FGF)23 in patients with acromegaly. Endocrine Journal 54 481-484. (doi:10.1507/endocrj. K06-217)
62. Itoh N & Ornitz DM 2011 Fibroblast growth factors: from molecular evolution to roles in development, metabolism and disease. Journal of Biochemistry 149 121-130. (doi:10.1093/jb/mvq121)
63. Junnila RK, List EO, Berryman DE, Murrey JW & Kopchick JJ 2013 The GH/IGF-1 axis in ageing and longevity. Nature Reviews. Endocrinology 9 366-376. (doi:10.1038/nrendo.2013.67)
64. Kamenicky P, Blanchard A, Gauci C, Salenave S, Letierce A, Lombes M, Brailly-Tabard S, Azizi M, Prie D, Souberbielle JC et al. 2012 Pathophysiology of renal calcium handling in acromegaly: what lies behind hypercalciuria? Journal of Clinical Endocrinology and Metabolism 97 2124-2133. (doi:10.1210/jc.2011-3188)
65. Kashimada K, Yamashita T, Tsuji K, Nifuji A, Mizutani S, Nabeshima Y & Noda M 2002 Defects in growth and bone metabolism in Klotho mutant mice are resistant to GH treatment. Journal of Endocrinology 174 403-410. (doi:10.1677/joe.0.1740403)
66. Kato Y, Arakawa E, Kinoshita S, Shirai A, Furuya A, Yamano K, Nakamura K, Iida A, Anazawa H, Koh N et al. 2000 Establishment of the anti-Klotho monoclonal antibodies and detection of Klotho protein in kidneys. Biochemical and Biophysical Research Communications 267 597-602. (doi:10.1006/bbrc.0999.2009)
67. Kawai M, Kinoshita S, Kimoto A, Hasegawa Y, Miyagawa K, Yamazaki M, Ohata Y, Ozono K & Michigami T 2013 FGF23 suppresses chondrocyte proliferation in the presence of soluble α-Klotho both in vitro and in vivo. Journal of Biological Chemistry 288 2414-2427. (doi:10.1074/jbc. M112.410043)
68. Khosravi A, Cutler CM, Kelly MH, Chang R, Royal RE, Sherry RM, Wodajo FM, Fedarko NS & Collins MT 2007 Determination of the elimination half-life of fibroblast growth factor-23. Journal of Clinical Endocrinology and Metabolism 92 2374-2377. (doi:10.1210/jc. 2006-2865)
69. Kim HR, Nam BY, Kim DW, Kang MW, Han JH, Lee MJ, Shin DH, Doh FM, Koo HM, Ko KI et al. 2013 Circulating α-Klotho levels in CKD and relationship to progression. American Journal of Kidney Diseases 61 899-909. (doi:10.1053/j.ajkd.2013.01.024)
70. Koh N, Fujimori T, Nishiguchi S, Tamori A, Shiomi S, Nakatani T, Sugimura K, Kishimoto T, Kinoshita S, Kuroki T et al. 2001 Severely reduced production of Klotho in human chronic renal failure kidney. Biochemical and Biophysical Research Communications 280 1015-1020. (doi:10.1006/bbrc.2000.4226)
71. Kohler S, Tschopp O, Sze L, Neidert M, Bernays RL, Spanaus KS, Wiesli P & Schmid C 2013 Monitoring for potential residual disease activity by serum insulin-like growth factor 1 and soluble Klotho in patients with acromegaly after pituitary surgery: is there an impact of the genomic deletion of exon 3 in the growth hormone receptor (d3-GHR) gene on "safe" GH cut-off values? General and Comparative Endocrinology 188 282-287. (doi:10.1016/j.ygcen.2013.04.024)
72. Komaba H, Goto S, Fujii H, Hamada Y, Kobayashi A, Shibuya K, Tominaga Y, Otsuki N, Nibu K, Nakagawa K et al. 2010 Depressed expression of Klotho and FGF receptor 1 in hyperplastic parathyroid glands from uremic patients. Kidney International 77 232-238. (doi:10.1038/ki.2009.414)
73. Krajisnik T, Bjorklund P, Marsel R, Ljunggren O, Akerstrom G, Jonsson KB, Westin G & Larsson TE 2007 Fibroblast growth factor-23 regulates parathyroid hormone and 1aα-hydroxylase expression in cultured bovine parathyroid cells. Journal of Endocrinology 195 125-131. (doi:10.1677/JOE-07-0267)
74. Krajisnik T, Olauson H, Mirza MA, Hellman P, Akerstrom G, Westin G, Larsson TE & Bjorklund P 2010 Parathyroid Klotho and FGF-receptor 1 expression decline with renal function in hyperparathyroid patients with chronic kidney disease and kidney transplant recipients. Kidney International 78 1024-1032. (doi:10.1038/ki.2010.260)
75. Kuro-o M 2010 Klotho. Pflügers Archiv 459 333-343. (doi:10.1007/ s00424-009-0722-7)
76. Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E et al. 1997 Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390 45-51. (doi:10.1038/36285)
77. Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, McGuinness OP, Chikuda H, Yamaguchi M, Kawaguchi H et al. 2005 Suppression of aging in mice by the hormone Klotho. Science 309 1829-1833. (doi:10.1126/science.1112766)
78. Kurosu H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, Rosenblatt KP, Baum MG, Schiavi S, Hu MC, Moe OW et al. 2006 Regulation of fibroblast growth factor-23 signaling by Klotho. Journal of Biological Chemistry 281 6120-6123. (doi:10.1074/jbc.C500457200)
79. 2+ channel to maintain endothelial integrity. PNAS 107 19308-09313. (doi:10.1073/pnas.1008544107)
80. Laron Z, Anin S, Klipper-Aurbach Y & Klinger B 1992 Effects of insulin-like growth factor on linear growth, head circumference, and body fat in patients with Laron-type dwarfism. Lancet 339 1258-1261. (doi:10.1016/0140-6736(92)91594-X)
81. Larsson T, Marsell R, Schipani E, Ohlsson C, Ljunggren O, Tenenhouse HS, Juppner H & Jonsson KB 2004 Transgenic mice expressing fibroblast growth factor 23 under the control of the α1(I) collagen promoter exhibit growth retardation, osteomalacia, and disturbed phosphate homeostasis. Endocrinology 145 3087-3094. (doi:10.1210/en.2003-1768)
82. Lau WL, Pai A, Moe SM & Giachelli CM 2011 Direct effects of phosphate on vascular cell function. Advances in Chronic Kidney Disease 18 105-112. (doi:10.1053/j.ackd.2010.12.002)
83. Lau WL, Leaf EM, Hu MC, Takeno MM, Kuro-oM, MoeOW& Giachelli CM 2012 Vitamin D receptor agonists increase Klotho and osteopontin while decreasing aortic calcification in mice with chronic kidney disease fed a high phosphate diet. Kidney International 82 1261-1270. (doi:10.1038/ki.2012.322)
84. Li SA, Watanabe M, Yamada H, Nagai A, Kinuta M & Takei K 2004 Immunohistochemical localization of Klotho protein in brain, kidney, and reproductive organs of mice. Cell Structure and Function 29 91-99. (doi:10.1247/csf.29.91)
85. Lindberg K, Olauson H, Amin R, Ponnusamy A, Goetz R, Taylor RF, Mohammadi M, Canfield A, Kublickiene K & Larsson TE 2013 Arterial Klotho expression and FGF23 effects on vascular calcification and function. PLoS ONE 8 e60658. (doi:10.1371/journal.pone.0060658)
86. Liu H, Fergusson MM, Castilho RM, Liu J, Cao L, Chen J, Malide D, Rovira II, Schimel D, Kuo CJ et al. 2007 Augmented Wnt signaling in a mammalian model of accelerated aging. Science 317 803-806. (doi:10.1126/science.1143578)
87. Lorenzi O, Veyrat-Durebex C, Wollheim CB, Villemin P, Rohner-Jeanrenaud F, Zanchi A & Vischer UM 2010 Evidence against a direct role of Klotho in insulin resistance. Pflügers Archiv 459 465-473. (doi:10.1007/s00424-009-0735-2)
88. Lund B, Eskildsen PC, Norman AW & Sorensen OH 1981 Calcium and vitamin D metabolism in acromegaly. Acta Endocrinologica 96 444-450. (doi:10.1530/acta.0.0960444)
89. Maekawa Y, Ohishi M, Ikushima M, Yamamoto K, Yasuda O, Oguro R, Yamamoto-Hanasaki H, Tatara Y, Takeya Y & Rakugi H 2011 Klotho protein diminishes endothelial apoptosis and senescence via a mitogen-activated kinase pathway. Geriatrics & Gerontology International 11 510-516. (doi:10.1111/j.1447-0594.2011.00699.x)
90. Majumdar V, Nagaraja D & Christopher R 2010 Association of the functional KL-VS variant of Klotho gene with early-onset ischemic stroke. Biochemical and Biophysical Research Communications 403 412-416. (doi:10.1016/j.bbrc.2010.11.045)
91. Mangos S, Amaral AP, Faul C, Juppner H, Reiser J & WolfM2012 Expression of fgf23 and αKlotho in developing embryonic tissues and adult kidney of the zebrafish, Danio rerio. Nephrology, Dialysis, Transplantation 27 4314-4322. (doi:10.1093/ndt/gfs335)
92. Manya H, Akasaka-Manya K & Endo T 2010 Klotho protein deficiency and aging. Geriatrics & Gerontology International 10(Suppl 1) S80-S87. (doi:10.1111/j.1447-0594.2010.00596.x)
93. Martin A, David V & Quarles LD 2012 Regulation and function of the FGF23/Klotho endocrine pathways. Physiological Reviews 92 131-155. (doi:10.1152/physrev.00002.2011)
94. Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M & Nabeshima Y 1998 Identification of the human klotho gene and its two transcripts encoding membrane and secreted Klotho protein. Biochemical and Biophysical Research Communications 242 626-630. (doi:10.1006/bbrc. 1997.8009)
95. Mitani H, Ishizaka N, Aizawa T, Ohno M, Usui S, Suzuki T, Amaki T, Mori I, Nakamura Y, Sato M et al. 2002 In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage. Hypertension 39 838-843. (doi:10.1161/01.HYP.0000013734.33441.EA)
96. Mori K, Yahata K, Mukoyama M, Suganami T, Makino H, Nagae T, Masuzaki H, Ogawa Y, Sugawara A, Nabeshima Y et al. 2000 Disruption of klotho gene causes an abnormal energy homeostasis in mice. Biochemical and Biophysical Research Communications 278 665-670. (doi:10.1006/bbrc.2000.3864)
97. Morishita K, Shirai A, Kubota M, Katakura Y, Nabeshima Y, Takeshige K & Kamiya T 2001 The progression of aging in klotho mutant mice can be modified by dietary phosphorus and zinc. Journal of Nutrition 131 3182-3188.
98. Nabeshima Y & Imura H 2008 α-Klotho: a regulator that integrates calcium homeostasis. American Journal of Nephrology 28 455-464. (doi:10.1159/ 000112824)
99. Nagai T, Yamada K, Kim HC, Kim YS, Noda Y, Imura A, Nabeshima Y & Nabeshima T 2003 Cognition impairment in the genetic model of aging klotho gene mutantmice: a role of oxidative stress. FASEB Journal 17 50-52. (doi:10.1096/fj.02-0448fje)
100. Nagasu H, Satoh M, Kuwabara A, Yorimitsu D, Kidokoro K, Nishi Y, Tomita N, Sasaki T & Kashihara N 2011 Overexpression of Klotho protein modulates uninephrectomy-induced compensatory renal hypertrophy by suppressing IGF-I signals. Biochemical and Biophysical Research Communications 407 39-43. (doi:10.1016/j.bbrc.2011.02.089)
101. Nakatani T, Sarraj B, Ohnishi M, Densmore MJ, Taguchi T, Goetz R, Mohammadi M, Lanske B & Razzaque MS 2009 In vivo genetic evidence for Klotho-dependent, fibroblast growth factor 23 (Fgf23)-mediated regulation of systemic phosphate homeostasis. FASEB Journal 23 433-441. (doi:10.1096/fj.08-114397)
102. Neidert MC, Sze L, Zwimpfer C, Sarnthein J, Seifert B, Frei K, Leske H, Rushing EJ, Schmid C & Bernays RL 2013 Soluble α-Klotho: a novel serum biomarker for the activity of GH-producing pituitary adenomas. European Journal of Endocrinology 168 575-583. (doi:10.1530/ EJE-12-1045)
103. Ohata Y, Arahori H, Namba N, Kitaoka T, Hirai H, Wada K, Nakayama M, Michigami T, Imura A, Nabeshima Y et al. 2011 Circulating levels of soluble α-Klotho are markedly elevated in human umbilical cord blood. Journal of Clinical Endocrinology and Metabolism 96 E943-E947. (doi:10.1210/jc.2010-2357)
104. Ohnishi M, Nakatani T, Lanske B & Razzaque MS 2009 Reversal of mineral ion homeostasis and soft-tissue calcification of klotho knockout mice by deletion of vitamin D 1α-hydroxylase. Kidney International 75 1166-1172. (doi:10.1038/ki.2009.24)
105. Ohyama Y, Kurabayashi M, Masuda H, Nakamura T, Aihara Y, Kaname T, Suga T, Arai M, Aizawa H, Matsumura Y et al. 1998 Molecular cloning of rat klotho cDNA: markedly decreased expression of klotho by acute inflammatory stress. Biochemical and Biophysical Research Communications 251 920-925. (doi:10.1006/bbrc.0998.9576)
106. Olauson H, Lindberg K, Amin R, Jia T, Wernerson A, Andersson G& Larsson TE 2012 Targeted deletion of Klotho in kidney distal tubule disrupts mineral metabolism. Journal of the American Society of Nephrology 23 1641-1651. (doi:10.1681/ASN.2012010048)
107. Osuka S & Razzaque MS 2012 Can features of phosphate toxicity appear in normophosphatemia?. Journal of Bone and Mineral Metabolism 30 10-18. (doi:10.1007/s00774-011-0343-z)
108. Park SJ, Park SH, Chang JW, Choi J, Jung HH & ImGJ 2012 Protective effect of klotho protein against cisplatin ototoxicity in an auditory cell line. Journal of Laryngology and Otology 126 1003-1009. (doi:10.1017/ S0022215112001715)
109. Park SJ, Shin EJ, Min SS, An J, Li Z, Hee Chung Y, Hoon Jeong J, Bach JH, Nah SY, Kim WK et al. 2013 Inactivation of JAK2/STAT3 signaling axis and downregulation of M1 mAChR cause cognitive impairment in klotho mutant mice, a genetic model of aging. Neuropsychopharmacology 38 1426-1437. (doi:10.1038/npp.2013.39)
110. Pavik I, Jaeger P, Ebner L, Poster D, Krauer F, Kistler AD, Rentsch K, Andreisek G, Wagner CA, Devuyst O et al. 2012 Soluble klotho and autosomal dominant polycystic kidney disease. Clinical Journal of the American Society of Nephrology 7 248-257. (doi:10.2215/ CJN.09020911)
111. Pavik I, Jaeger P, Ebner L, Wagner CA, Petzold K, Spichtig D, Poster D, Wuthrich RP, Russmann S & Serra AL 2013 Secreted Klotho and FGF23 in chronic kidney disease stage 1 to 5: a sequence suggested from a cross-sectional study. Nephrology, Dialysis, Transplantation 28 352-359. (doi:10.1093/ndt/gfs460)
112. Pedersen L, Pedersen SM, Brasen CL & Rasmussen LM 2013 Soluble serum Klotho levels in healthy subjects. Comparison of two different immunoassays. Clinical Biochemistry 46 1079-1083. (doi:10.1016/ j.clinbiochem.2013.05.046)
113. Pierson RWJr & Temin HM0972 The partial purification from calf serum of a fraction with multiplication-stimulating activity for chicken fibroblasts in cell culture and with non-suppressible insulin-like activity. Journal of Cellular Physiology 79 309-330. (doi:10.1002/jcp.1040790302)
114. Polanska UM, Edwards E, Fernig DG & Kinnunen TK 2011 The cooperation of FGF receptor and Klotho is involved in excretory canal development and regulation of metabolic homeostasis in Caenorhabditis elegans. Journal of Biological Chemistry 286 5657-5666. (doi:10.1074/jbc.M110. 173039)
115. Prader A, Illig R, Uehlinger E & Stalder G 1959 Rachitis infolge Knochentumors [Rickets following bone tumor]. Helvetica Paediatrica Acta 14 554-565.
116. Quigley R & Baum M 1991 Effects of growth hormone and insulin-like growth factor I on rabbit proximal convoluted tubule transport. Journal of Clinical Investigation 88 368-374. (doi:10.1172/JCI115312)
117. Rakugi H, Matsukawa N, Ishikawa K, Yang J, Imai M, Ikushima M, Maekawa Y, Kida I, Miyazaki J & Ogihara T 2007 Anti-oxidative effect of Klotho on endothelial cells through cAMP activation. Endocrine 31 82-87. (doi:10.1007/s12020-007-0016-9)
118. RazzaqueMS 2012 The role of Klotho in energy metabolism. Nature Reviews. Endocrinology 8 579-587. (doi:10.1038/nrendo.2012.75)
119. Rinderknecht E & Humbel RE 1978 The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. Journal of Biological Chemistry 253 2769-2776.
120. Rutishauser J, Schmid C, Hauri C, Froesch ER & Zapf J 1993 Growth hormone, but not insulin-like growth factor I, induces a serum protease activity for insulin-like growth factor binding protein-3 in hypophysectomized rats in vivo. FEBS Letters 334 23-26. (doi:10.1016/0014-5793(93)81672-M)
121. Saftig P & Reiss K 2011 The "A Disintegrin And Metalloproteases" ADAM10 and ADAM17: novel drug targets with therapeutic potential? European Journal of Cell Biology 90 527-535. (doi:10.1016/j.ejcb.2010.11.005)
122. Saito Y, Yamagishi T, Nakamura T, Ohyama Y, Aizawa H, Suga T, Matsumura Y, Masuda H, Kurabayashi M, Kuro-o M et al. 1998 Klotho protein protects against endothelial dysfunction. Biochemical and Biophysical Research Communications 248 324-329. (doi:10.1006/bbrc. 1998.8943)
123. Saito Y, Nakamura T, Ohyama Y, Suzuki T, Iida A, Shiraki-Iida T, Kuro-o M, Nabeshima Y, Kurabayashi M & Nagai R 2000 In vivo klotho gene delivery protects against endothelial dysfunction in multiple risk factor syndrome. Biochemical and Biophysical Research Communications 276 767-772. (doi:10.1006/bbrc.2000.3470)
124. +-dependent phosphate co-transport activity and 1a,25-dihydroxyvitamin D3 production. Journal of Biological Chemistry 278 2206-2211. (doi:10.1074/jbc.M207872200)
125. Salmon WD Jr & Daughaday WH 1957 A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. Journal of Laboratory and Clinical Medicine 49 825-836.
126. Sathyanesan M, Girgenti MJ, Banasr M, Stone K, Bruce C, Guilchicek E, Wilczak-Havill K, Nairn A, Williams K, Sass S et al. 2012 A molecular characterization of the choroid plexus and stress-induced gene regulation. Translational Psychiatry 2 e139. (doi:10.1038/tp.2012.64)
127. Satoh M, Nagasu H, Morita Y, Yamaguchi TP, Kanwar YS & Kashihara N 2012 Klotho protects against mouse renal fibrosis by inhibiting Wnt signaling. American Journal of Physiology. Renal Physiology 303 F1641-F1651. (doi:10.1152/ajprenal.00460.2012)
128. Schmid C &Meili E 2000 Acromegaly in a hemophilic patient infected with the hepatitis C and human immunodeficiency viruses. American Journal of Medicine 108 757-758. (doi:10.1016/S0002-9343(00)00421-6)
129. Schmid C, Rutishauser J, Schlapfer I, Froesch ER & Zapf J 1991 Intact but not truncated insulin-like growth factor binding protein-3 (IGFBP-3) blocks IGF I-induced stimulation of osteoblasts: control of IGF signalling to bone cells by IGFBP-3-specific proteolysis? Biochemical and Biophysical Research Communications 179 579-585. (doi:10.1016/0006-291X(91)91410-E)
130. Schoenle E, Zapf J, Humbel RE & Froesch ER 1982 Insulin-like growth factor I stimulates growth in hypophysectomized rats. Nature 296 252-253. (doi:10.1038/296252a0)
131. Scialla JJ, Lau WL, Reilly MP, Isakova T, Yang HY, Crouthamel MH, Chavkin NW, Rahman M, Wahl P, Amaral AP et al. 2013 Fibroblast growth factor 23 is not associated with and does not induce arterial calcification. Kidney International 83 1159-1168. (doi:10.1038/ki.2013.3)
132. Segawa H, Yamanaka S, Ohno Y, Onitsuka A, Shiozawa K, Aranami F, Furutani J, Tomoe Y, Ito M, Kuwahata M et al. 2007 Correlation between hyperphosphatemia and type II Na-Pi cotransporter activity in klotho mice. American Journal of Physiology. Renal Physiology 292 F769-F779. (doi:10.1152/ajprenal.00248.2006)
133. Seiler S, Wen M, Roth HJ, Fehrenz M, Flugge F, Herath E, Weihrauch A, Fliser D & Heine GH 2013 Plasma Klotho is not related to kidney function and does not predict adverse outcome in patients with chronic kidney disease. Kidney International 83 121-128. (doi:10.1038/ki.2012.288)
134. Semba RD, Cappola AR, Sun K, Bandinelli S, Dalal M, Crasto C, Guralnik JM & Ferrucci L 2011 Plasma klotho and mortality risk in older community-dwelling adults. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 66 794-800. (doi:10.1093/gerona/glr058)
135. Semba RD, Cappola AR, Sun K, Bandinelli S, Dalal M, Crasto C, Guralnik JM & Ferrucci L 2012 Relationship of low plasma klotho with poor grip strength in older community-dwelling adults: the InCHIANTI study. European Journal of Applied Physiology 112 1215-1220. (doi:10.1007/ s00421-011-2072-3)
136. Shalhoub V, Ward SC, Sun B, Stevens J, Renshaw L, Hawkins N & Richards WG 2011 Fibroblast growth factor 23 (FGF23) and α-Klotho stimulate osteoblastic MC3T3.E1 cell proliferation and inhibit mineralization. Calcified Tissue International 89 140-150. (doi:10.1007/ s00223-011-9501-5)
137. Shimada T, Mizutani S, Muto T, Yoneya T, Hino R, Takeda S, Takeuchi Y, Fujita T, Fukumoto S & Yamashita T 2001 Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. PNAS 98 6500-6505. (doi:10.1073/pnas.101545098)
138. Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, Fujita T, Nakahara K, Fukumoto S & Yamashita T 2004a FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. Journal of Bone and Mineral Research 19 429-435. (doi:10.1359/JBMR. 0301264)
139. Shimada T, Kakitani M, Yamazaki Y, Hasegawa H, Takeuchi Y, Fujita T, Fukumoto S, Tomizuka K & Yamashita T 2004b Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. Journal of Clinical Investigation 113 561-568. (doi:10.1172/JCI200409081)
140. Shimada T, Urakawa I, Yamazaki Y, Hasegawa H, Hino R, Yoneya T, Takeuchi Y, Fujita T, Fukumoto S & Yamashita T 2004c FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type IIa. Biochemical and Biophysical Research Communications 314 409-414. (doi:10.1016/j.bbrc. 2003.12.102)
141. Shiozaki M, Yoshimura K, Shibata M, Koike M, Matsuura N, Uchiyama Y & Gotow T 2008 Morphological and biochemical signs of age-related neurodegenerative changes in klotho mutant mice. Neuroscience 152 924-941. (doi:10.1016/j.neuroscience.2008.01.032)
142. Shiraki-Iida T, Aizawa H, Matsumura Y, Sekine S, Iida A, Anazawa H, Nagai R, Kuro-o M & Nabeshima Y 1998 Structure of the mouse klotho gene and its two transcripts encoding membrane and secreted protein. FEBS Letters 424 6-10. (doi:10.1016/S0014-5793(98)00127-6)
143. Shiraki-Iida T, Iida A, Nabeshima Y, Anazawa H, Nishikawa S, Noda M & Kuro-o M 2000 Improvement of multiple pathophysiological phenotypes of klotho (kl/kl) mice by adenovirus-mediated expression of the klotho gene. Journal of Gene Medicine 2 233-242. (doi:10.1002/ 1521-2254(200007/08)2:4<233::AID-JGM110O3.0.CO>2-5)
144. Shuto E, Taketani Y, Tanaka R, Harada N, Isshiki M, Sato M, Nashiki K, Amo K, Yamamoto H, Higashi Y et al. 2009 Dietary phosphorus acutely impairs endothelial function. Journal of the American Society of Nephrology 20 1504-1512. (doi:10.1681/ASN.2008101106)
145. Siahanidou T, Garatzioti M, Lazaropoulou C, Kourlaba G, Papassotiriou I, Kino T, Imura A, Nabeshima Y & Chrousos G 2012 Plasma soluble α-Klotho protein levels in premature and term neonates: correlations with growth and metabolic parameters. European Journal of Endocrinology 167 433-440. (doi:10.1530/EJE-12-0476)
146. Smith RC, O'Bryan LM, Farrow EG, Summers LJ, Clinkenbeard EL, Roberts JL, Cass TA, Saha J, Broderick C, Ma YL et al. 2012 Circulating aKlotho influences phosphate handling by controlling FGF23 production. Journal of Clinical Investigation 122 4710-4715. (doi:10.1172/JCI64986)
147. Sugano Y & Lardelli M 2011 Identification and expression analysis of the zebrafish orthologue of Klotho. Development Genes and Evolution 221 179-186. (doi:10.1007/s00427-011-0367-3)
148. Sugiura H, Tsuchiya K & Nitta K 2011 Circulating levels of soluble α-Klotho in patients with chronic kidney disease. Clinical and Experimental Nephrology 15 795-796. (doi:10.1007/s10157-011-0511-4)
149. Sugiura H, Yoshida T, Shiohira S, Kohei J, Mitobe M, Kurosu H, Kuro-o M, Nitta K & Tsuchiya K 2012 Reduced Klotho expression level in kidney aggravates renal interstitial fibrosis. American Journal of Physiology. Renal Physiology 302 F1252-F1264. (doi:10.1152/ajprenal.00294.2011)
150. Sze L, Bernays RL, Zwimpfer C, Wiesli P, Brandle M & Schmid C 2012 Excessively high soluble Klotho in patients with acromegaly. Journal of Internal Medicine 272 93-97. (doi:10.1111/j.1365-2796.2012.02542.x)
151. Takamoto S, Tsuchiya H, Onishi T, Morimoto S, Imanaka S, Mori S, Seino Y, Uozumi T & Kumahara Y 1985 Changes in calcium homeostasis in acromegaly treated by pituitary adenomectomy. Journal of Clinical Endocrinology and Metabolism 61 7-11. (doi:10.1210/jcem-61-1-7)
152. Takenaka T, Watanabe Y, Inoue T, Miyazaki T & Suzuki H 2013 Fibroblast growth factor 23 enhances renal klotho abundance. Pflügers Archiv 465 935-943. (doi:10.1007/s00424-013-1226-z)
153. Takeshita K, Fujimori T, Kurotaki Y, Honjo H, Tsujikawa H, Yasui K, Lee JK, Kamiya K, Kitaichi K, Yamamoto K et al. 2004 Sinoatrial node dysfunction and early unexpected death of mice with a defect of klotho gene expression. Circulation 109 1776-1782. (doi:10.1161/01.CIR. 0000124224.48962.32)
154. Tomiyama K, Maeda R, Urakawa I, Yamazaki Y, Tanaka T, Ito S, Nabeshima Y, Tomita T, Odori S, Hosoda K et al. 2010 Relevant use of Klotho in FGF09 subfamily signaling system in vivo. PNAS 107 1666-1671. (doi:10.1073/pnas.0913986107)
155. Tonelli M, Sacks F, Pfeffer M, Gao Z & Curhan G 2005 Relation between serum phosphate level and cardiovascular event rate in people with coronary disease. Circulation 112 2627-2633. (doi:10.1161/ CIRCULATIONAHA.105.553098)
156. Tsujikawa H, Kurotaki Y, Fujimori T, Fukuda K & Nabeshima Y 2003 Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system. Molecular Endocrinology 17 2393-2403. (doi:10.1210/ me.2003-0048)
157. Ullrich A, Gray A, Tam AW, Yang-Feng T, Tsubokawa M, Collins C, Henzel W, Le Bon T, Kathuria S, Chen E et al. 1986 Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO Journal 5 2503-2512.
158. Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S & Yamashita T 2006 Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 444 770-774. (doi:10.1038/nature05315)
159. Utsugi T, Ohno T, Ohyama Y, Uchiyama T, Saito Y, Matsumura Y, Aizawa H, Itoh H, Kurabayashi M, Kawazu S et al. 2000 Decreased insulin production and increased insulin sensitivity in the klotho mutant mouse, a novel animal model for human aging. Metabolism 49 1118-1123. (doi:10.1053/meta.2000.8606)
160. Wang Y & Sun Z 2009 Klotho gene delivery prevents the progression of spontaneous hypertension and renal damage. Hypertension 54 810-817. (doi:10.1161/HYPERTENSIONAHA.109.134320)
161. Wang Y, Chen L, Huang G, He D, He J, Xu W, Zou C, Zong F, Li Y, Chen B et al. 2013 Klotho sensitizes human lung cancer cell line to cisplatin via PI3k/Akt pathway. PLoS ONE 8 e57391. (doi:10.1371/journal.pone. 0057391)
162. White KE, Cabral JM, Davis SI, Fishburn T, Evans WE, Ichikawa S, Fields J, Yu X, Shaw NJ, McLellan NJ et al. 2005 Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation. American Journal of Human Genetics 76 361-367. (doi:10.1086/427956)
163. White HD, Ahmad AM, Durham BH, Chandran S, Patwala A, Fraser WD & Vora JP 2006 Effect of active acromegaly and its treatment on parathyroid circadian rhythmicity and parathyroid target-organ sensitivity. Journal of Clinical Endocrinology and Metabolism 91 913-909. (doi:10.1210/jc.2005-1602)
164. Wolf I, Levanon-Cohen S, Bose S, Ligumsky H, Sredni B, Kanety H, Kuro-o M, Karlan B, Kaufman B, Koeffler HP et al. 2008 Klotho: a tumor suppressor and a modulator of the IGF-1 and FGF pathways in human breast cancer. Oncogene 27 7094-7105. (doi:10.1038/onc.2008.292)
165. Wu X, Weiszmann J, Ge H, Baribault H, Stevens J, Hawkins N, Vonderfecht S, Gardner J, Gupte J, Sheng J et al. 2012 A unique FGF23 with the ability to activate FGFR signaling through both αKlotho and βKlotho. Journal of Molecular Biology 418 82-89. (doi:10.1016/j.jmb. 2012.02.027)
166. Wu AL, Feng B, Chen MZ, Kolumam G, Zavala-Solorio J, Wyatt SK, Gandham VD, Carano RA & Sonoda J 2013 Antibody-mediated activation of FGFR1 induces FGF23 production and hypophosphatemia. PLoS ONE 8 e57322. (doi:10.1371/journal.pone.0057322)
167. Xiao NM, Zhang YM, Zheng Q & Gu J 2004 Klotho is a serum factor related to human aging. Chinese Medical Journal 117 742-747.
168. Yamamoto M, Clark JD, Pastor JV, Gurnani P, Nandi A, Kurosu H, Miyoshi M, Ogawa Y, Castrillon DH, Rosenblatt KP et al. 2005 Regulation of oxidative stress by the anti-aging hormone klotho. Journal of Biological Chemistry 280 38029-38034. (doi:10.1074/jbc.M509039200)
169. Yamamoto KT, Robinson-CohenC, de Oliveira MC, Kostina A,Nettleton JA, Ix JH, Nguyen H, Eng J, Lima JA, Siscovick DS et al. 2013 Dietary phosphorus is associated with greater left ventricular mass. Kidney International 83 707-714. (doi:10.1038/ki.2012.303)
170. Yamashita T, Yoshioka M& Itoh N 2000 Identification of a novel fibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain. Biochemical and Biophysical Research Communications 277 494-498. (doi:10.1006/bbrc.2000.3696)
171. Yamazaki Y, Imura A, Urakawa I, Shimada T, Murakami J, Aono Y, Hasegawa H, Yamashita T, Nakatani K, Saito Y et al. 2010 Establishment of sandwich ELISA for soluble α-Klotho measurement: age-dependent change of soluble α-Klotho levels in healthy subjects. Biochemical and Biophysical Research Communications 398 513-518. (doi:10.1016/j.bbrc. 2010.06.110)
172. Yoshida T, Fujimori T & Nabeshima Y 2002 Mediation of unusually high concentrations of 1,25-dihydroxyvitamin D in homozygous klotho mutant mice by increased expression of renal 1α-hydroxylase gene. Endocrinology 143 683-689. (doi:10.1210/en.143.2.683)
173. Zapf J, Morell B, Walter H, Laron Z & Froesch ER 1980 Serum levels of insulin-like growth factor (IGF) and its carrier protein in various metabolic disorders. Acta Endocrinologica 95 505-517. (doi:10.1530/ acta.0.0950505)
174. Zapf J, Walter H & Froesch ER 1981 Radioimmunological determination of insulin-like growth factors I and II in normal subjects and in patients with growth disorders and extrapancreatic tumor hypoglycemia. Journal of Clinical Investigation 68 1321-1330. (doi:10.1172/ JCI110379)
175. Zhou L, Li Y, Zhou D, Tan RJ & Liu Y 2013 Loss of Klotho contributes to kidney injury by derepression of Wnt/β-catenin signaling. Journal of the American Society of Nephrology 24 771-785. (doi:10.1681/ASN. 2012080865)
176. Zhu Y, Xu L, Zhang J, Xu W, Liu Y, Yin H, Lv T, An H, Liu L, He H et al. 2013 Klotho suppresses tumor progression via inhibiting PI3K/Akt/GSK3β/Snail signaling in renal cell carcinoma. Cancer Science 104 663-671. (doi:10.1111/cas.12134)
177. Zoidis E, Gosteli-Peter M, Ghirlanda-Keller C, Meinel L, Zapf J & Schmid C 2002 IGF-I and GH stimulate Phex mRNA expression in lungs and bones and 1,25-dihydroxyvitamin D(3) production in hypophysectomized rats. European Journal of Endocrinology 146 97-105. (doi:10.1530/eje.0.1460097)
178. Zoidis E, Ghirlanda-Keller C, Gosteli-Peter M, Zapf J & Schmid C 2004 Regulation of phosphate (Pi) transport and NaPi-III transporter (Pit-1) mRNA in rat osteoblasts. Journal of Endocrinology 181 531-540. (doi:10.1677/joe.0.1810531)