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ID 117147
タイトル別表記
25-ヒドロキシビタミンD-1α-水酸化酵素は異所性石灰化を誘導する
著者
イマム, イリムラティ 徳島大学大学院栄養生命科学教育部(人間栄養科学専攻)
Ohtani, Ayako Tokushima University
Takei, Yuichiro University of Kochi
Furuichi, Airi Tokushima University
Miyazaki, Makoto University of Colorado Anschutz Medical Campus
キーワード
hyperphosphatemia
medial calcification
arteriosclerosis
chronic kidney disease
bone and mineral disease
dialysis
資料タイプ
学位論文
抄録
Vascular calcification is an important pathogenesis related to cardiovascular disease and high mortality rate in chronic kidney disease (CKD) patients. It has been well-known that hyper­phosphatemia induces osteochondrogenic transition of vascular smooth muscle cells (VSMCs) resulting ectopic calcification in aortic media, cardiac valve, and kidney. However, the detailed mechanism of the ectopic calcification has been not clarified yet. Here, we found that the co-localization of CYP27B1 with the calcified lesions of aorta and arteries in kidney of klotho mutant (kl/kl) mice, and then investigated the role of CYP27B1 in the mineralization of the VSMCs. Under high phosphate condition, overexpression of CYP27B1 induced calcification and osteocalcin mRNA expression in the VSMCs. Inversely, siRNA-CYP27B1 inhibited high phosphate-induced calcification of the VSMCs. We also found that the accumulated CYP27B1 protein was glycosylated in the kidney of kl/kl mice. Therefore, overexpression of CYP27B1-N310A and CYP27B1-T439A, which are a mutation for N-linked glycosylation site (N310A) and a mutation for O-linked glycosylation site (T439A) in CYP27B1, decreased calcium deposition and expression of RUNX2 induced by high phosphate medium in VSMCs compared with wild-type CYP27B1. These results suggest that extra-renal expression of glycosylated CYP27B1 would be required for ectopic calcification of VSMCs under hyperphosphatemia.
掲載誌名
Journal of Clinical Biochemistry and Nutrition
ISSN
09120009
18805086
cat書誌ID
AA10710201
出版者
Society for Free Radical Research Japan
71
2
開始ページ
103
終了ページ
111
発行日
2022-06-04
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Yilimulati Yimamuの学位論文として提出され,学位審査・授与の対象となっている。
権利情報
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (https://creativecommons.org/licenses/by-nc-nd/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
博士論文全文を含む
文科省報告番号
甲第3636号
学位記番号
甲栄第291号
学位授与年月日
2022-03-24
学位名
博士(栄養学)
学位授与機関
徳島大学
部局
医学系