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Literature DB >> 27890549

Novel functions of circulating Klotho.

Julia M Hum¹, Linda O'Bryan², Rosamund C Smith², Kenneth E White³.

Abstract

A significant portion of the key biological functions of αKlotho (αKL) and its cognate ligand Fibroblast growth factor-23 (FGF23) have been revealed through the study of rare diseases of mineral metabolism. These findings have far reaching implications for common disorders such as chronic kidney disease-mineral bone disorder (CKD-MBD). αKL's predominant effect on mineral homeostasis is through its actions in the kidney as a co-receptor for FGF23, however emerging data has shed light on its capacity to act as a circulating factor through the cleavage of the transmembrane form of αKL ('mKL') to produce 'cleaved KL' or 'cKL'. This review summarizes new findings from studies using extended delivery of cKL to mouse models with phenotypes reflecting those arising in CKD-MBD.

Entities: Chemical Disease Gene Mutation Species

Keywords: FGF23; Hyperphosphatemia; Hypophosphatemia; Phosphate; Vascular calcification; cKL

Mesh：

Substances：

Year: 2016 PMID： 27890549 PMCID： PMC5441975 DOI： 10.1016/j.bone.2016.11.025

Source DB: PubMed Journal: Bone ISSN： 1873-2763 Impact factor: 4.398

49 in total

1. Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule.

Authors: Ming Chang Hu; Mingjun Shi; Jianning Zhang; Johanne Pastor; Teruyo Nakatani; Beate Lanske; M Shawkat Razzaque; Kevin P Rosenblatt; Michel G Baum; Makoto Kuro-o; Orson W Moe
Journal: FASEB J Date: 2010-05-13 Impact factor: 5.191

Review 2. Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism.

Authors: Ming Chang Hu; Kazuhiro Shiizaki; Makoto Kuro-o; Orson W Moe
Journal: Annu Rev Physiol Date: 2013 Impact factor: 19.318

3. A novel GALNT3 mutation in a pseudoautosomal dominant form of tumoral calcinosis: evidence that the disorder is autosomal recessive.

Authors: Shoji Ichikawa; Kenneth W Lyles; Michael J Econs
Journal: J Clin Endocrinol Metab Date: 2005-02-01 Impact factor: 5.958

4. Molecular cloning and expression analyses of mouse betaklotho, which encodes a novel Klotho family protein.

Authors: S Ito; S Kinoshita; N Shiraishi; S Nakagawa; S Sekine; T Fujimori; Y I Nabeshima
Journal: Mech Dev Date: 2000-11 Impact factor: 1.882

5. A novel mutation in fibroblast growth factor 23 gene as a cause of tumoral calcinosis.

Authors: Kaori Araya; Seiji Fukumoto; Rebecca Backenroth; Yasuhiro Takeuchi; Kounosuke Nakayama; Nobuaki Ito; Nozomi Yoshii; Yuji Yamazaki; Takeyoshi Yamashita; Justin Silver; Takashi Igarashi; Toshiro Fujita
Journal: J Clin Endocrinol Metab Date: 2005-07-19 Impact factor: 5.958

6. Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis.

Authors: Orit Topaz; Daniel L Shurman; Reuven Bergman; Margarita Indelman; Paulina Ratajczak; Mordechai Mizrachi; Ziad Khamaysi; Doron Behar; Dan Petronius; Vered Friedman; Israel Zelikovic; Sharon Raimer; Arieh Metzker; Gabriele Richard; Eli Sprecher
Journal: Nat Genet Date: 2004-05-09 Impact factor: 38.330

7. Progressive vascular calcification over 2 years is associated with arterial stiffening and increased mortality in patients with stages 4 and 5 chronic kidney disease.

Authors: Mhairi K Sigrist; Maarten W Taal; Peter Bungay; Christopher W McIntyre
Journal: Clin J Am Soc Nephrol Date: 2007-10-10 Impact factor: 8.237

8. Diabetic eNOS knockout mice develop distinct macro- and microvascular complications.

Authors: Sumathy Mohan; Robert L Reddick; Nicolas Musi; Diane A Horn; Bo Yan; Thomas J Prihoda; Mohan Natarajan; Sherry L Abboud-Werner
Journal: Lab Invest Date: 2008-04-07 Impact factor: 5.662

9. Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population.

Authors: Majd A I Mirza; Anders Larsson; Håkan Melhus; Lars Lind; Tobias E Larsson
Journal: Atherosclerosis Date: 2009-05-21 Impact factor: 5.162

10. The high prevalence of chronic kidney disease-mineral bone disorders: A hospital-based cross-sectional study.

Authors: B Ghosh; T Brojen; S Banerjee; N Singh; S Singh; O P Sharma; J Prakash
Journal: Indian J Nephrol Date: 2012-07

12 in total

1. FGF23-klotho axis, bone fractures, and arterial stiffness in dialysis: a case-control study.

Authors: L-C Desbiens; A Sidibé; R-V Ung; C Fortier; M Munger; Y-P Wang; S-K Bisson; K Marquis; M Agharazii; F Mac-Way
Journal: Osteoporos Int Date: 2018-06-29 Impact factor: 4.507

2. Beclin 1/Bcl-2 complex-dependent autophagy activity modulates renal susceptibility to ischemia-reperfusion injury and mediates renoprotection by Klotho.

Authors: Peng Li; Mingjun Shi; Jenny Maique; Joy Shaffer; Shirley Yan; Orson W Moe; Ming Chang Hu
Journal: Am J Physiol Renal Physiol Date: 2020-01-27

Review 3. Klotho: An Elephant in Aging Research.

Authors: Amin Cheikhi; Aaron Barchowsky; Amrita Sahu; Sunita N Shinde; Abish Pius; Zachary J Clemens; Hua Li; Charles A Kennedy; Joerg D Hoeck; Michael Franti; Fabrisia Ambrosio
Journal: J Gerontol A Biol Sci Med Sci Date: 2019-06-18 Impact factor: 6.053

Novel functions of circulating Klotho.

1. Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule.

Review 2. Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism.

3. A novel GALNT3 mutation in a pseudoautosomal dominant form of tumoral calcinosis: evidence that the disorder is autosomal recessive.

4. Molecular cloning and expression analyses of mouse betaklotho, which encodes a novel Klotho family protein.

5. A novel mutation in fibroblast growth factor 23 gene as a cause of tumoral calcinosis.

6. Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis.

7. Progressive vascular calcification over 2 years is associated with arterial stiffening and increased mortality in patients with stages 4 and 5 chronic kidney disease.

8. Diabetic eNOS knockout mice develop distinct macro- and microvascular complications.

9. Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population.

10. The high prevalence of chronic kidney disease-mineral bone disorders: A hospital-based cross-sectional study.

1. FGF23-klotho axis, bone fractures, and arterial stiffness in dialysis: a case-control study.

2. Beclin 1/Bcl-2 complex-dependent autophagy activity modulates renal susceptibility to ischemia-reperfusion injury and mediates renoprotection by Klotho.

Review 3. Klotho: An Elephant in Aging Research.

Review 4. The Emerging Key Role of Klotho in the Hypothalamus-Pituitary-Ovarian Axis.

5. FGF23 expression is stimulated in transgenic α-Klotho longevity mouse model.

Review 6. Fibroblast growth factor 23 and α-Klotho co-dependent and independent functions.

Review 7. Upstream Regulators of Fibroblast Growth Factor 23.

Review 8. Renal Contributions to Age-Related Changes in Mineral Metabolism.

9. In search of alternatively spliced alpha-Klotho Kl1 protein in mouse brain.

Review 10. FGF23 Actions on Target Tissues-With and Without Klotho.