组蛋白去乙酰化酶在间充质干细胞C3H10T1/2成脂分化过程中的表达及HDAC11的作用  

A Role of HDAC11 in Adipogenic Differentiation among Mesenchymal Stem Cells C3H10TI /2 Expressed HDACs

作　　者：黄晓迪[1] 王奎栋[1] 季秋虹[2] 颜民[3] 季煜华[1] 季菊玲[3] 

机构地区：[1]暨南大学生命科学技术学院组织移植与免疫实验中心,广州510632 [2]南通大学附属医院神经内科,江苏南通226001 [3]南通大学医学院病理系,江苏南通226001

出　　处：《中国生物化学与分子生物学报》2015年第12期1330-1336,共7页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No.81201016,No.81272027,No.81141048)资助~~

摘　　要：组蛋白去乙酰化酶(histone deacetylase,HDAC)通过调节组蛋白乙酰化修饰参与调控基因表达.研究发现多种HDAC参与成脂分化,但其机制尚不清楚.本研究探讨间充质干细胞C3H10T1/2成脂分化过程中HDAC的表达变化及其对成脂分化的影响.本研究首先建立了C3H10T1/2体外成脂分化的模型,并以油红O染色鉴定成功诱导成脂分化.PCR检测C3H10T1/2细胞成脂分化过程中11种HDAC的变化趋势,发现成脂分化过程中,HDAC1、2、5、9和10的m RNA表达量下降,而HDAC3、6、8和11的m RNA表达量明显上升,其中HDAC11上升最为显著.进一步通过RNA干扰沉默HDAC11表达,PCR检测成脂分化的关键转录因子PPARγ2和成脂标志物Perilipin、Adipoq的m RNA表达量下降,但Fabp4表达变化不明显.油红O染色结果表明,诱导C3H10T1/2成脂分化过程中,干扰HDAC11表达,胞浆内脂滴形成数量减少,成脂分化受到抑制.实验结果提示,C3H10T1/2细胞成脂分化伴随着多种HDAC表达的变化,其中HDAC11的增加最显著,干扰HDAC11的表达可以抑制C3H10T1/2细胞的成脂分化.Histone deacetylase （HDAC） regulates gene expression by controlling histone acetylation. It has been reported that HDACs participated in adipogenic differentiation, but the underlying mechanisms were less understood. To study the effects of HDACs on adipogenic differentiation, oil red O staining was used for the assay of adipogenesls of mesenchymal stem cells C3H10TI/2 in vitro. RT-PCR was used to detect the changes in the expression of HDACll during adipogenic differentiation, and the results showed large differences in the expression levels of each kind. HDAC3, 6, 8 and 11 were increased significantly （with HDACll as the most）, while HDAC1, 2, 5, 9 and 10 were decreased. No obvious change was observed for Fabp4. Transfection of siRNA-HDAC11 suppressedadipogenetic differentiation with down-regulated level of the key adipogenic transcription factor of PPARγ2, and adipogenic markers of perilipin and adipoq. In conclusion, the expression of HDACs varied during the adipogenic differentiation of C3H10T1/2, and increased expression of HDACll might facilitate adipogenesis.

关 键 词：间充质干细胞 成脂分化 组蛋白去乙酰化酶 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学] R589.2[医药卫生—基础医学]