粒细胞集落刺激因子对辐射诱导间充质干细胞远期损伤的作用及其基因芯片分析  

Microarray analysis and the effect of G-CSF on ionizing radiation induced long term mesenchymal stem cells injury

作　　者：黄颂[1] 邢永华[1] 张俊伶[1] 路璐[1] 李程程[1] 李德冠[1] 孟爱民[1] 

机构地区：[1]北京协和医学院中国医学科学院放射医学研究所,天津300192

出　　处：《中国医药导报》2015年第9期9-13,共5页China Medical Herald

基　　金：国家自然科学基金海外合作基金项目(编号81129020);国家自然科学基金面上项目(编号81372928);国家重点基础研究发展计划项目("973"计划)(编号2011CB964800-G)

摘　　要：目的研究粒细胞集落刺激因子(Granulocyte colony-stimulating factor,G-CSF)对辐射诱导间充质干细胞(MSCs)远期损伤的作用及其可能分子机制。方法将30只SPF级C57BL/6雌性小鼠均分为对照组、6 Gy照射组、6 Gy照射+G-CSF组。获取各组小鼠MSCs细胞后进行全基因表达基因芯片分析。对差异表达的基因进行基因本体功能分类分析,并在京都基因和基因组百科全书生物信息数据库中进行通路富集分析。结果经6 Gy照射后小鼠MSCs中表达上调最显著的20个基因中,有12个基因在6 Gy+G-CSF组小鼠MSCs中表达下调(Vangl1、L1cam、Hdac2、Polk、Id1、Ttc37、Afp、Ccnb1、Ikbkg、Mad1l1、Itgb3、Rrm2)。经6 Gy照射后小鼠MSCs中表达下调的所有基因中,有10个基因在6 Gy+G-CSF组小鼠MSCs中的表达上调(Ccl19、Ccl21a、G6pc2、Igf1、Tnnt2、Ifna6、Tnfrsf14、Il13、Acaca、Oxsm)。以上基因主要富集在细胞因子及其受体间相互作用通路、细胞凋亡及细胞周期调节通路、PI3K-Akt信号通路、NF-κB信号通路、p53信号通路中。结论 G-CSF可能对辐射诱导MSCs远期损伤有修复作用,其分子机制可能与调节细胞周期、抑制细胞凋亡、促进细胞分化及促进免疫应答有关。Objective To study the effect of G-CSF on ionizing radiation（IR） induced long term mesenchymal stem cells（MSCs） injury and its possible molecular mechanisms. Methods 30 SPF C57BL/6 female mice were divided into control group, 6 Gy irradiation Group, 6 Gy irradiation ＋ G-CSF administration group equally, RNA of mice＇s MSCs was extracted from the mice of three groups, and then biotin-labeled c DNA was generated by reverse transcription of m RNA for hybridization with Roche Nimble Gen 12x135 K mouse gene expression microarrays. The differentially expressed genes with 2-fold change were identified. Gene ontology enrichment analysis and pathway analysis based on Kyoto Encyclopedia of genes and genomes database were used to distribute the differentially expressed genes into biological processes and pathways. Results Among top 20 of up-regulated genes in 6 Gy group compared to control group,12 genes were down-regulated in 6 Gy＋G-CSF group（Vangl1, L1 cam, Hdac2, Polk, Id1, Ttc37, Afp, Ccnb1, Ikbkg,Mad1l1, Itgb3, Rrm2）. 10 genes were up-regulated in 6 Gy＋G-CSF group while down-regulated in 6 Gy group（Ccl19,Ccl21 a, G6pc2, Igf1, Tnnt2, Ifna6, Tnfrsf14, Il13, Acaca, Oxsm）. Pathway analysis based on KEGG database showed all the differentially expressed genes described above were mainly associated with cytokine-cytokine receptor interaction pathway, cell cycle and cell apoptosis regulation pathway, PI3K-Akt signaling pathway, NF-κB signaling pathway and p53 signaling pathway. Conclusion G-CSF may repair the IR-induced long term MSCs damage, and its molecular mechanisms may relate to regulation of cell cycle, inhibition of cell apoptosis, promotion of cell differentiation, or improve the immune response. Further researches are required to clarify the related signal transduction pathways.

关 键 词：G-CSF 间充质干细胞 辐射 基因芯片 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]