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ID 117147
Title Alternative
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
Author
Yimamu, Yilimulati Tokushima University
Ohtani, Ayako Tokushima University
Takei, Yuichiro University of Kochi
Furuichi, Airi Tokushima University
Miyazaki, Makoto University of Colorado Anschutz Medical Campus
Keywords
hyperphosphatemia
medial calcification
arteriosclerosis
chronic kidney disease
bone and mineral disease
dialysis
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Journal of Clinical Biochemistry and Nutrition
ISSN
09120009
18805086
NCID
AA10710201
Publisher
Society for Free Radical Research Japan
Volume
71
Issue
2
Start Page
103
End Page
111
Published Date
2022-06-04
Remark
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。
Rights
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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3636号
Diploma Number
甲栄第291号
Granted Date
2022-03-24
Degree Name
Doctor of Nutritional Science
Grantor
Tokushima University
departments
Medical Sciences