Microtubule stabilization attenuates vascular calcification through the inhibition of osteogenic signaling and matrix vesicle release

Title
Microtubule stabilization attenuates vascular calcification through the inhibition of osteogenic signaling and matrix vesicle release
Author(s)
정대원이경희김현수
Keywords
SMOOTH-MUSCLE-CELLS; STAGE RENAL-DISEASE; CARDIOVASCULAR RISK; GENE-EXPRESSION; TAXOL; CYTOSKELETON; PHOSPHATE; DIFFERENTIATION; PACLITAXEL; MECHANISM
Issue Date
201408
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Citation
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.451, no.3, pp.436 - 441
Abstract
Vascular calcification is a strong predictor of cardiovascular morbidity and mortality, especially in individuals with chronic kidney disease or diabetes. The mechanism of vascular calcification has remained unclear, however, and no effective therapy is currently available. Our study was aimed at identifying the role of dynamic remodeling of microtubule cytoskeletons in hyperphosphatemia-induced vascular calcification. Exposure of primary cultures of mouse vascular smooth muscle cells (VSMCs) to inorganic phosphate (Pi) elicited ectopic calcification that was associated with changes in tubulin dynamics, induction of osteogenic signaling, and increased release of matrix vesicles. A microtubule depolymerizing agent enhanced Pi-dependent calcification, whereas microtubule stabilization by paclitaxel suppressed calcification both in VSMC cultures and in an ex vivo culture system for the mouse aorta. The inhibition of Pi-stimulated calcification by paclitaxel was associated with down-regulation of osteogenic signal and attenuation of matrix vesicle release. Our results indicate that microtubule plays a central role in vascular calcification, and that microtubule stabilization represents a potential new approach to the treatment of this condition. (C) 2014 Elsevier Inc. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/31315http://dx.doi.org/10.1016/j.bbrc.2014.08.007
ISSN
0006-291X
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의과대학 > 미생물학교실 > Articles
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