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 hyper-phosphatemia 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 () 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- inhibited high phosphate-induced calcification of the VSMCs. We also found that the accumulated CYP27B1 protein was glycosylated in the kidney of mice. Therefore, overexpression of CYP27B1-N310A and CYP27B1-T439A, which are a mutation for -linked glycosylation site (N310A) and a mutation for -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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| http://dx.doi.org/10.3164/jcbn.22-16 | DOI Listing |
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