Role of parathyroid hormone in Klotho-FGF23 system

Takaaki Kimura, Kazuhiro Shiizaki, Makoto Kuro-O

Research output: Contribution to journalArticle

Abstract

Klotho was originally identified as an anti-aging gene that accelerated aging when disrupted and extended life span when overexpressed in mice. The Klotho gene encodes a single-pass transmembrane protein and is expressed in the kidney and parathyroid gland. Klotho protein functions as an obligate subunit of the receptor for fibroblast growth factor 23 (FGF23). FGF23 is a hormone secreted from osteocytes and osteoblasts and acts on renal tubular cells to promote phosphate excretion into the urine and suppress synthesis of active form of vitamin D (1,25-dihydroxyvitamin D3;1,25(OH)(2)D(3)). Decreased Klotho expression due to the kidney damage including CKD might increase the circulating level of FGF23 and trigger disturbed mineral-bone metabolism, leading to CKD-MBD. Characteristic features of CKD-MBD including hyperphosphatemia, hypocalcemia, and decreased serum 1,25(OH)(2)D(3) can be explained by (mal) adaptation of the Klotho-FGF23 system, which also contributes to the pathophysiology of secondary hyperparathyroidism (SHPT). In addition to its function as a receptor for FGF23, the extracellular domain of Klotho is secreted by ectodomain shedding and functions as a humoral factor that regulates multiple ion channels and transporters. Thus, Klotho has emerged as a key regulator of mineral metabolism in health and disease.

Original languageEnglish (US)
Pages (from-to)859-866
Number of pages8
JournalClinical calcium
Volume26
Issue number6
StatePublished - Jun 1 2016

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Parathyroid Hormone
Chronic Kidney Disease-Mineral and Bone Disorder
Kidney
Minerals
Hyperphosphatemia
Osteocytes
Secondary Hyperparathyroidism
Parathyroid Glands
Hypocalcemia
Calcitriol
Osteoblasts
Ion Channels
Vitamin D
Genes
Phosphates
fibroblast growth factor 23
Urine
Hormones
Bone and Bones
Health

ASJC Scopus subject areas

  • Medicine(all)

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Kimura, T., Shiizaki, K., & Kuro-O, M. (2016). Role of parathyroid hormone in Klotho-FGF23 system. Clinical calcium, 26(6), 859-866.

Role of parathyroid hormone in Klotho-FGF23 system. / Kimura, Takaaki; Shiizaki, Kazuhiro; Kuro-O, Makoto.

In: Clinical calcium, Vol. 26, No. 6, 01.06.2016, p. 859-866.

Research output: Contribution to journalArticle

Kimura, T, Shiizaki, K & Kuro-O, M 2016, 'Role of parathyroid hormone in Klotho-FGF23 system', Clinical calcium, vol. 26, no. 6, pp. 859-866.
Kimura T, Shiizaki K, Kuro-O M. Role of parathyroid hormone in Klotho-FGF23 system. Clinical calcium. 2016 Jun 1;26(6):859-866.
Kimura, Takaaki ; Shiizaki, Kazuhiro ; Kuro-O, Makoto. / Role of parathyroid hormone in Klotho-FGF23 system. In: Clinical calcium. 2016 ; Vol. 26, No. 6. pp. 859-866.
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