Soluble Klotho causes hypomineralization in Klotho-deficient mice
Journal of Endocrinology 237 巻 3 号
285-300 頁
2018-06 発行
アクセス数 : 677 件
ダウンロード数 : 92 件
今月のアクセス数 : 5 件
今月のダウンロード数 : 2 件
この文献の参照には次のURLをご利用ください : https://ir.lib.hiroshima-u.ac.jp/00049037
| ファイル情報(添付) | |
| タイトル ( eng ) |
Soluble Klotho causes hypomineralization in Klotho-deficient mice
|
| 作成者 |
Aubin Jane E.
|
| 収録物名 |
Journal of Endocrinology
|
| 巻 | 237 |
| 号 | 3 |
| 開始ページ | 285 |
| 終了ページ | 300 |
| 抄録 |
The type I transmembrane protein αKlotho (Klotho) serves as a coreceptor for the phosphaturic hormone fibroblast growth factor 23 (FGF23) in kidney, while a truncated form of Klotho (soluble Klotho, sKL) is thought to exhibit multiple activities, including acting as a hormone, but whose mode(s) of action in different organ systems remains to be fully elucidated. FGF23 is expressed primarily in osteoblasts/osteocytes and aberrantly high levels in the circulation acting via signaling through an FGF receptor (FGFR)-Klotho coreceptor complex cause renal phosphate wasting and osteomalacia. We assessed the effects of exogenously added sKL on osteoblasts and bone using Klotho-deficient (kl/kl) mice and cell and organ cultures. sKL induced FGF23 signaling in bone and exacerbated the hypomineralization without exacerbating the hyperphosphatemia, hypercalcemia and hypervitaminosis D in kl/kl mice. The same effects were seen in rodent bone models in vitro, in which we also detected formation of a sKL complex with FGF23-FGFR and decreased Phex (gene responsible for X-linked hypophosphatemic rickets (XLH)/osteomalacia) expression. Further, sKL-FGF23-dependent hypomineralization in vitro was rescued by soluble PHEX. These data suggest that exogenously added sKL directly participates in FGF23 signaling in bone and that PHEX is a downstream effector of the sKL-FGF23-FGFR axis in bone.
|
| 著者キーワード |
FGF23
Klotho
Phex
kl/kl mice
|
| 内容記述 |
This work was supported in part by grants from the Ministry of Education, Science, Sports and Culture, Japan (18592001 and 20592139 to Y Y and 21791788 to T M), and the Canadian Institutes of Health Research (MOP 83704 to J E A).
|
| NDC分類 |
医学 [ 490 ]
|
| 言語 |
英語
|
| 資源タイプ | 学術雑誌論文 |
| 出版者 |
Society for Endocrinology
|
| 発行日 | 2018-06 |
| 権利情報 |
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Endocrinology, copyright © Society for Endocrinology after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1530/JOE-17-0683. This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認、ご利用ください。
|
| 出版タイプ | Author’s Original（十分な品質であるとして、著者から正式な査読に提出される版） |
| アクセス権 | オープンアクセス |
| 収録物識別子 |
[ISSN] 0022-0795
[ISSN] 1479-6805
[DOI] 10.1530/JOE-17-0683
[PMID] 29632215
[DOI] https://doi.org/10.1530/JOE-17-0683
|
| 備考 | Post-print version/PDF may be used in an institutional repository after an embargo period of 12 months. |
