Intestinal epithelial GR in the regulation of intestinal inflammation and colon cancer

The goal of this project is to investigate the role of glucocorticoids and their receptor, glucocorticoid receptor (GR), in intestinal stress response and tissue homeostasis. Using a mouse model with specific deletion of GR in intestinal epithelium (GR iKO mice), we recently discovered that intestinal epithelial GR deficiency deteriorates acute colitis while reducing chronic inflammation-associated colon cancer formation in mice. To understand the molecular mechanisms underlying these phenotypes, we examined colonic transcriptomes of Flox control and GR iKO mice treated with or without dextran sulfate sodium (DSS) for 7 days by microarray analysis. Total RNA were extracted from colon tissues of 4 pairs of regular Flox control and GR iKO mice and 3 pairs of Flox and GR iKO mice treated with 2.5% DSS in drinking water for 7 days. Gene expression profiles were analyzed using Agilent Whole Mouse Genome 4x44 multiplex format oligo arrays (014868) (Agilent Technologies, Santa Clara, CA), following the Agilent 1-color microarray-based gene expression analysis protocol.

本项目旨在探究糖皮质激素（glucocorticoids）及其受体糖皮质激素受体（glucocorticoid receptor, GR）在肠道应激反应与组织稳态中的作用。我们此前借助肠道上皮细胞特异性GR敲除小鼠模型（GR iKO小鼠）开展研究，发现肠道上皮GR缺失会加重小鼠急性结肠炎，同时却会抑制慢性炎症相关结直肠癌的发生发展。为解析上述表型背后的分子机制，我们通过微阵列分析，对经葡聚糖硫酸钠（dextran sulfate sodium, DSS）处理或未处理的Flox对照小鼠与GR iKO小鼠的结肠转录组进行了检测。我们从两类小鼠的结肠组织中提取总RNA：一类为4对未处理的常规Flox对照小鼠与GR iKO小鼠，另一类为3对经2.5% DSS饮水处理7天的同基因型小鼠。基因表达谱分析采用安捷伦（Agilent Technologies, 美国加利福尼亚州圣克拉拉）全小鼠基因组4x44多元阵列寡核苷酸芯片（货号014868，Agilent Whole Mouse Genome 4x44 multiplex format oligo arrays, 014868），并严格遵循安捷伦单色微阵列基因表达分析实验方案。