The role of LDLR in intestinal inflammation. The role of LDLR in intestinal inflammation

Low-density lipoprotein (LDL) is a risk factor for atherosclerosis, obesity, and other metabolic diseases, but its role in colitis is unknown. Here, we investigated the role of LDL in colitis by using LDL receptor deficient mice (Ldlr-/-). Wild-type and Ldlr-/- mice were fed with 3% DSS for 5 days and colons tissues were collected at day 8 post DSS treatment. We observed that Ldlr-/- mice are less susceptible to colitis. To understand the role of LDLR in colitis pathogenesis, we isolated RNA from colons of WT and Ldlr-/- mice and perfoemed RNA-seq. Our data show that the expression of inflamamtory genes are reduced in Ldlr-/- colons compared to wild-type. These data suggest that LDL is a potent endogenous trigger for intestinal inflammation. Overall design: Wild-type and Ldlr-Ko mice (male, 8-10 weels old) were administered with 3% DSS for 5 days. Colon tissues were collected at day 8 post DSS and RNA was isolated form the colons for RNA-seq analysis.

低密度脂蛋白（Low-density lipoprotein, LDL）是动脉粥样硬化、肥胖及其他代谢性疾病的危险因素，但其在结肠炎中的作用尚未明确。本研究以低密度脂蛋白受体缺陷小鼠（Ldlr-/-）为模型，探究LDL在结肠炎中的作用。将8-10周龄的雄性野生型（wild-type, WT）与Ldlr-/-小鼠喂食3%葡聚糖硫酸钠（Dextran Sulfate Sodium, DSS）5天，并于DSS处理后第8天采集结肠组织。实验观察到，Ldlr-/-小鼠对结肠炎的易感性更低。为阐明LDLR在结肠炎发病机制中的作用，我们从野生型与Ldlr-/-小鼠的结肠组织中提取RNA并进行RNA测序（RNA-seq）。数据分析表明，相较于野生型小鼠，Ldlr-/-小鼠结肠组织中的炎症基因表达水平显著降低。上述结果提示，LDL是肠道炎症的强效内源性触发因子。总体实验设计：选取8-10周龄的雄性野生型与Ldlr-Ko小鼠，给予3% DSS喂食5天，于DSS处理后第8天采集结肠组织，提取结肠RNA用于RNA-seq分析。