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学科主题基础医学
Phosphate-induced autophagy counteracts vascular calcification by reducing matrix vesicle release
Dai, Xiao-Yan1; Zhao, Ming-Ming1; Cai, Yan1; Guan, Qing-Cong2; Zhao, Ying3; Guan, Youfei1; Kong, Wei1; Zhu, Wei-Guo3; Xu, Ming-Jiang1; Wang, Xian1
关键词apoptosis autophagy chronic renal failure hyperphosphatemia oxidative stress
刊名KIDNEY INTERNATIONAL
2013-06-01
DOI10.1038/ki.2012.482
83期:6页:1042-1051
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Urology & Nephrology
资助者National Basic Research Program of China ; National Science &amp ; Technology Pillar Program ; National Natural Science Foundation of China ; Beijing Natural Science Foundation (Mammalian Target of Rapamycin Complex-1 (mTORC1) Promotes Vascular Smooth Muscle Cell Calcification) ; National Basic Research Program of China ; National Science &amp ; Technology Pillar Program ; National Natural Science Foundation of China ; Beijing Natural Science Foundation (Mammalian Target of Rapamycin Complex-1 (mTORC1) Promotes Vascular Smooth Muscle Cell Calcification)
研究领域[WOS]Urology & Nephrology
关键词[WOS]SMOOTH-MUSCLE-CELLS ; BETA-GLYCEROPHOSPHATE ; INORGANIC-PHOSPHATE ; PRIMARY CULTURE ; SELF-DIGESTION ; APOPTOSIS ; CALCIUM ; DISEASE ; GROWTH ; DEATH
英文摘要

Autophagy is a dynamic and highly regulated process of self-digestion responsible for cell survival and reaction to oxidative stress. As oxidative stress is increased in uremia and is associated with vascular calcification, we studied the role of autophagy in vascular calcification induced by phosphate. In an in vitro phosphate-induced calcification model of vascular smooth muscle cells (VSMCs) and in an in vivo model of chronic renal failure, autophagy was inhibited by the superoxide dismutase mimic MnTMPyP, superoxide dismutase-2 overexpression, and by knockdown of the sodium-dependent phosphate cotransporter Pit1. Although phosphate-induced VSMC apoptosis was reduced by an inhibitor of autophagy (3-methyladenine) and knockdown of autophagy protein 5, calcium deposition in VSMCs was increased during inhibition of autophagy, even with the apoptosis inhibitor Z-VAD-FMK. An inducer of autophagy, valproic acid, decreased calcification. Furthermore, 3-methyladenine significantly promoted phosphate-induced matrix vesicle release with increased alkaline phosphatase activity. Thus, autophagy may be an endogenous protective mechanism counteracting phosphate-induced vascular calcification by reducing matrix vesicle release. Therapeutic agents influencing the autophagic response may be of benefit to treat aging or disease-related vascular calcification and osteoporosis.

语种英语
所属项目编号2010CB912504 ; 2011CB503904 ; 2012BAI39B03 ; 81270370 ; 30900566 ; 81170099 ; 81121061 ; 31230035
资助者National Basic Research Program of China ; National Science &amp ; Technology Pillar Program ; National Natural Science Foundation of China ; Beijing Natural Science Foundation (Mammalian Target of Rapamycin Complex-1 (mTORC1) Promotes Vascular Smooth Muscle Cell Calcification) ; National Basic Research Program of China ; National Science &amp ; Technology Pillar Program ; National Natural Science Foundation of China ; Beijing Natural Science Foundation (Mammalian Target of Rapamycin Complex-1 (mTORC1) Promotes Vascular Smooth Muscle Cell Calcification)
WOS记录号WOS:000319740300013
引用统计
被引频次:55[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64155
专题基础医学院_心血管所
作者单位1.Peking Univ Hlth Sci Ctr, Sch Basic Med Sci, Key Lab Mol Cardiovasc Sci, Dept Physiol & Pathophysiol,Minist Educ, Beijing 100191, Peoples R China
2.Taizhou Municicpal Hosp, Div Renal, Taizhou, Peoples R China
3.Peking Univ Hlth Sci Ctr, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China
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Dai, Xiao-Yan,Zhao, Ming-Ming,Cai, Yan,et al. Phosphate-induced autophagy counteracts vascular calcification by reducing matrix vesicle release[J]. KIDNEY INTERNATIONAL,2013,83(6):1042-1051.
APA Dai, Xiao-Yan.,Zhao, Ming-Ming.,Cai, Yan.,Guan, Qing-Cong.,Zhao, Ying.,...&Wang, Xian.(2013).Phosphate-induced autophagy counteracts vascular calcification by reducing matrix vesicle release.KIDNEY INTERNATIONAL,83(6),1042-1051.
MLA Dai, Xiao-Yan,et al."Phosphate-induced autophagy counteracts vascular calcification by reducing matrix vesicle release".KIDNEY INTERNATIONAL 83.6(2013):1042-1051.
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