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博来霉素致C57小鼠肺纤维化分子靶点的探寻

Searching for Molecular Targets in Pulmonary Fibrosis Induced by Bleomycin in C57 Mouse

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【作者】 黄冬冬王尉平顾振纶蒋小岗周文轩郭次仪

【Author】 HUANG Dong-dong1,2,WANG Wei-ping1,2,GU Zhen-lun2,3,JIANG Xiao-gang2,3,ZHOU Wen-xuan2,4,GUO Ci-yi2,4 (1.Dept of Biochemistry and Molecular Biology,Medical College,Soochow University,Jiangsu Suzhou 215123,China;2.Suzhou Institute of Chinese Materia Medica,Jiangsu Suzhou 215007,China;3.Laboratory of Aging and Nervous Diseases,Soochow University,Jiangsu Suzhou 215123,China;4.the Hong Kong Association for Health Care,Hong Kong,China)

【机构】 苏州大学医学部生物化学与分子生物学系苏州中药研究所苏州大学衰老与神经疾病实验室香港保健协会

【摘要】 目的探寻博来霉素(BLM)致C57小鼠肺纤维化分子靶点。方法应用BRB-ArrayTools软件中justR-MA算法分析BLM(实验组)和生理盐水(对照组)作用于C57小鼠1、3、14d后肺组织基因表达谱数据集GSE485,找出差异表达基因;应用DAVID在线工具对这些基因进行功能聚类,结合《京都基因与基因组百科全书》和BioCar-ta进行生物学通路分析;应用MSigDB搜寻[-2kb,2kb]区域富集的转录因子结合位点。结果分别筛选出190、345、527个差异表达基因;按功能显著聚集的有趋化因子、膜蛋白、血清蛋白、补体成分、免疫球蛋白、钙黏蛋白、基质金属蛋白酶、前胶原类;受调控的有Toll样受体、CCR5、ECM受体、补体途径、TGF-β生物学通路;富集度较高的有AP1、SRF、NFKAPPAB转录因子。结论 AP1、SRF和RhoA可能是BLM致C57小鼠肺纤维化的分子靶点。

【Abstract】 Objective To Search for molecular targets in pulmonary fibrosis induced by bleomycin in C57 mouse.Methods Use the justRMA algorithm of BRB-ArrayTools software in search for differentially expressed genes on gene expression profile(GSE485) in bleomycin or saline treated C57 mice,which were sacrificed at 1day,3 and 14 days after injection.The online analyzing tool DAVID was applied to search for the functional classification of the differentlly expressed genes,and regulated pathways in KEGG and BioCarta database.MSigDB was applied to detect enriched transcription factor binding sites in[-2kb,2kb] of the differentlly expressed genes.Results Number of genes that passed filtering criteria:190,345 and 527.Gene groups,chemokines,membrane protein,serum protein,complement components,immunoglobulin,cadherin,matrix metalloproteinases,procollagen,was able to easily be indentified.Toll-like receptor,CCR5,ECM receptor,complement,TGF-β signaling pathways were regulated.Enriched transcription factor were AP1,SRF and NFKAPPAB.Conclusion AP1、SRF and RhoA may be the molecular targets in pulmonary fibrosis induced by bleomycin in C57 mice.

【基金】 香港保健协会资助项目(20050916-2HK)
  • 【文献出处】 苏州大学学报(医学版) ,Suzhou University Journal of Medical Science , 编辑部邮箱 ,2010年02期
  • 【分类号】R563
  • 【下载频次】238
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