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