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ID 113624
著者
Kinoshita, Yuka The University of Tokyo
髙士, 祐一 Tokushima University
Ito, Nobuaki The University of Tokyo
Ikegawa, Shiro RIKEN Center for Integrative Medical Sciences
Mano, Hiroyuki National Cancer Center Research Institute
Ushiku, Tetsuo The University of Tokyo
Fukayama, Masashi The University of Tokyo
Nangaku, Masaomi The University of Tokyo
キーワード
Tumor-induced osteomalacia (TIO)
Klotho
Fibroblast growth factor 23 (FGF23)
FGF receptor (FGFR)
Hypophosphatemia
資料タイプ
学術雑誌論文
抄録
Tumor-induced rickets/osteomalacia (TIO) is a rare paraneoplastic syndrome caused by tumors that ectopically express fibroblast growth factor 23 (FGF23). FGF23 is a bone-derived hormone that regulates serum phosphate concentrations. Patients with TIO develop hypophosphatemic rickets/osteomalacia due to FGF23 excess and suffer from symptoms such as leg deformities, bone pain, skeletal muscle myopathy, and multiple fractures/ pseudofractures. Usually, successful surgical removal of the causative tumors normalizes serum FGF23 and phosphate concentrations in patients with TIO. Most FGF23-producing tumors associated with TIO are histologically called phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT). The precise mechanism by which these tumors ectopically overproduce FGF23 outside of bone is yet to be clarified. Therefore, we performed an RNA sequencing analysis of a PMTMCT that was found in the left parotid gland of a patient with TIO. Among the upregulated genes, we focused on Klotho, the protein product of which is a single pass transmembrane protein that works along with an FGF receptor 1c as a receptor complex for FGF23. Subsequent histological analysis confirmed the ectopic expression of Klotho in other PMTMCTs. From these results, we assume that the ectopic expression of Klotho in PTMMCTs enables a positive feedback loop in FGF23 production via the activation of FGF receptor 1c and exacerbates disease manifestations in TIO.
掲載誌名
Bone Reports
ISSN
23521872
出版者
Elsevier
10
開始ページ
100192
発行日
2018-12-31
権利情報
© 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
先端酵素学研究所