HDAC1基因沉默和HIF-1α过表达改善MSCs定向分化及VEGF分泌的功能  

HDAC1 silencing and HIF-1αover-expression improve differentiation and VEGF paracrine of MSCs

作　　者：汤穆浛 卢俊江 韩敦正[3] TANG Mu-han;LU Jun-jiang;HAN Dun-zheng(Emergency Department of Guangzhou Red Cross Hospital,Guangzhou 510220,China;Guangzhou Chest Hospital,Guangzhou 510095,China;Department of Cardiology,The First Affiliated Hospital of Guangzhou Medical University,Guangzhou 510120,China)

机构地区：[1]广州市红十字会医院急诊科,广东广州510220 [2]广州市胸科医院,广东广州510095 [3]广州医科大学附属第一医院心血管内科,广东广州510120

出　　处：《中国病理生理杂志》2021年第9期1668-1672,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金面上项目(No.81570258);广东省医学科学技术研究基金资助项目(No.A2020178)。

摘　　要：目的:探讨低氧诱导因子1α(hypoxia inducible factor-1α,HIF-1α)过表达对组蛋白脱乙酰酶1(histone deacetylase 1,HDAC1)基因沉默大鼠间充质干细胞(mesenchymal stem cells,MSCs)血管内皮生长因子(vascular endothelial growth factor,VEGF)分泌功能的影响。方法:用全骨髓贴壁法,从大鼠骨髓中提取MSCs,HDAC1-shRNA慢病毒感染MSCs,用嘌呤霉素筛选出稳定细胞株,再予以重组腺病毒HIF-1α三突变体(recombinant adenovirus containing triple-point mutant HIF-1αgene,Ad-HIF-1α-trip)感染HDAC1-shRNA-MSCs使其过表达HIF-1α,分别用RT-qPCR及Western blot检测MSCs中HIF-1α及VEGF的表达量。结果:HIF-1α过表达后,HDAC1基因沉默的MSCs中HIF-1α及VEGF的表达量均显著升高(P<0.05)。结论:HIF-1α过表达可改善HDAC1基因沉默大鼠MSCs中HIF-1α的表达及VEGF的分泌功能。AIM:To investigate a method to improve vascular endothelial growth factor(VEGF)secretion function of mesenchymal stem cells(MSCs)with histone deacetylase 1(HDAC1)silencing by over-expressing hypoxia-inducible factor-1α(HIF-1α).METHODS:The MSCs,separated from rat bone marrow,were transfected by the lentivirus carrying HDAC1-shRNA and purified with purinomycin.The recombinant adenovirus containing triple-point mutant HIF-1αgene(Ad-HIF-1α-trip)was then used to over-express HIF-1αin HDAC1-shRNA-MSCs.The expression levels of HIF-1αand VEGF in the MSCs were detected by RT-qPCR and Western blot.RESULTS:The HIF-1αand VEGF expression levels in HDAC1-shRNA-MSCs were significantly increased after over-expression of HIF-1α(P<0.05).CONCLUSION:Over-expression of HIF-1αimproves VEGF secretion function of rat MSCs with HDAC1 silencing.

关 键 词：低氧诱导因子1Α 组蛋白脱乙酰酶1 间充质干细胞 血管内皮生长因子 

分 类 号：R329.21[医药卫生—人体解剖和组织胚胎学] R363.2[医药卫生—基础医学]