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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。
Objective To investigate the molecular target of pulmonary fibrosis induced by bleomycin (BLM) in C57 mice. Methods The gene expression profiles of GSE485 in lung tissues of C57 mice treated with BLM (experimental group) and saline (control group) were analyzed by justR-MA algorithm in BRB-ArrayTools software to find differentially expressed genes. The genes were clustered using DAVID online tools, and biological pathways were analyzed with the “Kyoto Encyclopedia of Gene and Genome” and BioCar-ta. MS-PCR was used to search for the transcription factor binding site rich in [-2kb, 2kb] regions. RESULTS: A total of 190,345,527 differentially expressed genes were screened, and chemokines, membrane proteins, serum proteins, complement components, immunoglobulins, cadherins, matrix metalloproteinases and procollagen were clustered according to their functions. There are Toll-like receptors, CCR5, ECM receptors, complement pathway and TGF-β biological pathway regulated by APS. AP1, SRF and NFKAPPAB transcription factors are highly enriched. Conclusion AP1, SRF and RhoA may be the molecular targets of pulmonary fibrosis induced by BLM in C57 mice.