| 特集名 | 副甲状腺疾患とその病態 | |
|---|---|---|
| 題名 | 副甲状腺機能亢進症におけるFGF-23-Klotho系の意義 | |
| 発刊年月 | 2013年 11月 | |
| 著者 | 椎崎 和弘 | Department of Pathology, The University of Texas Southwestern Medical Center at Dallas |
| 著者 | 黒尾 誠 | Department of Pathology, The University of Texas Southwestern Medical Center at Dallas |
| 【 要旨 】 | Klothoやfibroblast growth factor 23（FGF-23）はリンやビタミンDをおもな標的にして骨ミネラル代謝の重要な役割を担っている．この調節機構の破綻は慢性腎臓病に伴う骨ミネラル代謝異常（CKD-MBD）の発症に大きく影響している．CKD-MBDの所見の一つが二次性副甲状腺機能亢進症（SHPT）であり，この病態には腎障害に特徴的なKlothoやFGF-23の変化が関与している． KlothoはFGF receptorと複合体を形成し，FGF-23のシグナルに必須であるため，CKDの腎臓ではKlotho発現の減少が血液中のFGF-23値の上昇をもたらす．これがビタミンDを抑制し副甲状腺機能亢進症を導く．CKDの早期では，機能するネフロン数の減少をFGF-23や副甲状腺ホルモン（PTH）の上昇により代償し，リンやカルシウムの恒常性を保っている． 副甲状腺でもKlothoやFGF-23によるPTHの分泌を調節する機序が明らかになりつつあり，CKD-MBDでのPTH過剰分泌に関与していると考えられている． |
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| Theme | Parathyroid diseases and their pathogenesis | |
|---|---|---|
| Title | Role of FGF-23-Klotho in hyperparathyroidism | |
| Author | Kazuhiro Shiizaki | Department of Pathology, The University of Texas Southwestern Medical Center at Dallas |
| Author | Makoto Kuro-o | Department of Pathology, The University of Texas Southwestern Medical Center at Dallas |
| [ Summary ] | Klotho and FGF-23 play important roles in bone and mineral metabolism including endocrine regulation of phosphate and vitamin D metabolism. CKD-induced adaptation of this endocrine axis may contribute to secondary hyperparathyroidism. Klotho is essential for FGF-23 signaling as a co-receptor of FGF receptor. Decreased Klotho expression levels in the kidneys may increase circulating FGF-23 levels. FGF-23 suppresses the activation of vitamin D, resulting in secondary hyperparathyroidism. In the early stages of CKD, increased FGF-23 and PTH levels compensate for decreased functional nephron numbers to maintain the homeostasis of phosphate and calcium. Recent studies have revealed that PTH is also regulated by Klotho and FGF-23. It is proposed that resistance of the parathyroid glands to FGF-23 may contribute to secondary hyperparathyroidism. |
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