MicroRNA-378＊通过抑制CTGF促进人骨髓间充质干细胞凋亡  

MicroRNA-378* enhances apoptosis of human mesenchymal stem cells by repressing expression of CTGF

作　　者：董珺[1,2] 曾波航[1] 刘宁宁[2] 莫沛[3] 熊龙根[3,2] 刘世明[3,2] 黎佼[3,2] 

机构地区：[1]广州医科大学附属第二医院肿瘤科,广东广州510260 [2]广州医科大学附属第二医院广州心血管疾病研究所,广东广州510260 [3]广州医科大学附属第二医院心内科,广东广州510260

出　　处：《中国病理生理杂志》2014年第12期2238-2242,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金青年项目(No.81401156);广州市属高校科研计划项目(No.2012C232);广州医科大学博士科研项目(No.2012C42)

摘　　要：目的:研究年龄相关microRNA-378*(miR-378*)对人骨髓间充质干细胞(h MSCs)存活和凋亡的调控作用。方法:通过microRNA芯片和qRT-PCR检测供体年龄对h MSCs中miR-378*表达的影响;通过H2O2诱导h MSCs凋亡;通过转染miR-378*模拟物或抑制物,过表达或抑制miR-378*的表达;用MTT、LDH、caspase-3/7、TUNEL检测等方法研究其对h MSCs存活和凋亡的影响;通过siRNA研究结缔组织生长因子(CTGF)对h MSCs存活和凋亡的影响。结果:随供体年龄增加,h MSCs中miR-378*的表达增加。H2O2刺激可促进miR-378*表达,抑制CTGF表达。过表达miR-378*可减少h MSCs的存活,促进细胞凋亡。相反,抑制miR-378*的表达促进h MSCs的存活,减少细胞凋亡。同时抑制miR-378*和CTGF的表达,使miR-378*失去对h MSCs存活和凋亡的调控作用。直接抑制CTGF的表达可减少h MSCs的存活,促进细胞凋亡。结论:miR-378*通过抑制CTGF的表达减少h MSCs存活,促进h MSCs凋亡。AIM： To investigate the effects of microRNA-378 ＊ （ miR-378 ＊ ） on the survival and apoptosis of human mesenchymal stem cells （hMSCs）. METHODS： The expression of miR-378 ＊ was determined by microRNA arrays and quantitative real-time PCR （qRT-PCR）. H202 was used to induce hMSCs apoptosis. By transfection of miR- 378 ＊ mimic or inhibitor, we up-regulated or down-regulated miR-378 ＊ expression in hMSCs. The effect of miR-378 ＊ and connective tissue growth factor （CTGF） on hMSC survival and apoptosis were detected by MTI＇, LDH, caspase-3/7 and TUNEL assays. RESULTS： The expression of miR-378 ＊ was up-regulated in the old hMSCs compared with the young hMSCs. H202 increased the expression of miR-378 ＊ , decreased the expression of CTGF. Up-regulation of miR-378 ＊ re- suited in increasing apoptosis and decreasing survival of hMSCs. Conversely, down-regulation of miR-378 ＊ resulted in de- creasing cell apoptosis and increasing survival. The regulation of miR-378 ＊ on hMSC apoptosis and survival was attenuated by inhibiting the expression of miR-378 ＊ and CTGF together. Direct repression of CTGF expression inhibited the hMSC survival and increased apoptosis. CONCLUSION： miR-378 ＊ enhances apoptosis of hMSCs by repressing the expression of CTGF.

关 键 词：人骨髓间充质干细胞 MicroRNA-378＊ 细胞凋亡 

分 类 号：R363[医药卫生—病理学]