Department of Pathology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana 71103, USA.
Physiol Genomics. 2011 Jan 7;43(1):43-56. doi: 10.1152/physiolgenomics.00138.2010. Epub 2010 Oct 5.
Dextran sodium sulfate (DSS)-induced colitis is widely used to study pathological mechanisms and potential treatments of inflammatory bowel disease. Because temporal changes in genome expression profiles remain unknown in this model, we performed whole genome expression profile analysis during the development of DSS colitis in comparison with ulcerative colitis (UC) specimens to identify novel and common responses during disease. Colon tissue from DSS-treated mice was collected at days 0, 2, 4, and 6. Half of each specimen was used for histopathological analysis and half for Affymetrix whole genome expression profiling and qRT-PCR validation. Genesifter and Ingenuity software analysis was used to identify differentially expressed genes and perform interactive network analysis. Identified DSS-associated genes in mice were also compared with UC patient data. We identified 1,609 genes that were significantly altered during DSS colitis; the majority were functionally related to inflammation, angiogenesis, metabolism, biological adhesion, cellular growth and proliferation, and cell-to-cell signaling responses. Five hundred and one genes were progressively upregulated, while one hundred seventy-three genes were progressively downregulated. Changes in gene expression were validated in a subset of 33 genes by qRT-PCR, with r(2) = 0.925. Ingenuity gene interaction network analysis revealed novel relationships among antigen presentation, cell morphology, and other biological functions in the DSS mouse. Finally, DSS colitis gene array data were compared with UC patient array data: 152 genes were similarly upregulated, and 22 genes were downregulated. Temporal genomewide expression profile analysis of DSS-induced colitis revealed novel associations with various immune responses and tissue remodeling events such as angiogenesis similar to those in UC patients. This study provides a comprehensive view of DSS colitis changes in colon gene expression and identifies common molecules with clinical specimens that are interesting targets for further investigation.
硫酸葡聚糖钠（DSS）诱导的结肠炎广泛用于研究炎症性肠病的病理机制和潜在治疗方法。由于在该模型中，基因组表达谱的时间变化尚不清楚，因此我们在 DSS 结肠炎的发展过程中与溃疡性结肠炎（UC）标本进行了全基因组表达谱分析，以鉴定疾病过程中的新的和共同的反应。用 DSS 处理的小鼠的结肠组织分别在第 0、2、4 和 6 天收集。每个标本的一半用于组织病理学分析，另一半用于 Affymetrix 全基因组表达谱分析和 qRT-PCR 验证。使用 Genesifter 和 Ingenuity 软件分析来识别差异表达的基因并进行交互网络分析。还将在小鼠中鉴定的与 DSS 相关的基因与 UC 患者数据进行比较。我们鉴定了在 DSS 结肠炎中显著改变的 1609 个基因；其中大多数与炎症、血管生成、代谢、生物粘附、细胞生长和增殖以及细胞间信号反应有关。501 个基因逐渐上调，而 173 个基因逐渐下调。通过 qRT-PCR 验证了 33 个基因的子集的表达变化，r(2)=0.925。Ingenuity 基因相互作用网络分析揭示了 DSS 小鼠中抗原呈递、细胞形态和其他生物学功能之间的新关系。最后，将 DSS 结肠炎基因阵列数据与 UC 患者的阵列数据进行比较：152 个基因相似上调，22 个基因下调。DSS 诱导的结肠炎的时间基因组表达谱分析揭示了与各种免疫反应和组织重塑事件（如血管生成）的新关联，与 UC 患者相似。本研究提供了 DSS 结肠炎中结肠基因表达变化的全面视图，并确定了与临床标本的共同分子，这些分子是进一步研究的有趣目标。
