中山大学学报（医学科学版）2018，Vol.39Issue(3)：329-334,6.
中性鞘磷脂酶2/神经酰胺调节高磷高钙诱导的血管平滑肌细胞成骨样分化和钙化
nSMase2/ceramide Regulates High Calcium and Phosphate-Induced Osteogenic Differentiation and Calcification of Vascular Smooth Muscle Cells
摘要
Abstract
[Objective] Vascular calcification is a gene-regulated biological process similar to bone formation.It is very common in the patients with chronic kidney disease.Neutral sphingomyelinase 2 (nSMase2) is a key regulator of bone development,and is responsible for ceramide generation through sphingomyelin hydrolysis,but the role of nSMase2 in vascular calcification remains unclear.The aim of this study is to determine whether nSMase2 regulates high calcium and phosphate-induced calcification of vascular smooth muscle cells (VSMC).[Methods] In vitro model of human VSMC calcification was used in this study and high calcium and phosphate were used to induce calcification of VSMCs.GW4869 was used to inhibit nSMase2 activity and nSMase2 was knockdowned in cultured VSMC using nSMase2 siRNA.The expression of Runx2,BMP2 and Osterix was analyzed by qRT-PCR and calcification was assessed by alizarin red staining.[Results] We found that nSMase2 expression and ceramide levels were increased in the process of VSMC calcification (P＜0.05).Inhibition of nSMase2 activity by GW4869 and knockdown of nSMase2 attenuated high calcium and phosphate-induced VSMC calcification and down-regulated the expression level of Runx2,BMP2 and Osterix (P＜0.05).By contrast,ceramide accelerated rat VSMC calcification and increased ALP activity (P＜0.05).[Conclusion] We demonstrate that nSMase2/ceramide promotes high calcium and phosphate-induced VSMC calcification,suggesting that nSMase2/ceramide could participate in the progression of vascular calcification in patients with chronic kidney disease.关键词
血管钙化/血管平滑肌细胞/鞘磷脂酶2/成骨样分化Key words
vascular calcification/vascular smooth muscle cells/neutral sphingomyelinase 2/osteogenic differentiation分类
医药卫生引用本文复制引用
梁青春,宋艳,陈燕亭,陆立鹤..中性鞘磷脂酶2/神经酰胺调节高磷高钙诱导的血管平滑肌细胞成骨样分化和钙化[J].中山大学学报（医学科学版）,2018,39(3):329-334,6.基金项目
国家自然科学基金(81000124) （81000124）
广东省自然科学基金(2016A030313226,2015A030312009) （2016A030313226,2015A030312009）
