Department of Medicine and Biological Chemistry, University of California, Irvine, CA, USA.
Dev Biol. 2010 Feb 15;338(2):270-9. doi: 10.1016/j.ydbio.2009.12.008. Epub 2009 Dec 16.
Anterior Gradient 2 (AGR2) is a protein disulfide isomerase that plays important roles in diverse processes in multiple cell lineages as a developmental regulator, survival factor and susceptibility gene for inflammatory bowel disease. Here, we show using germline and inducible Agr2-/- mice that Agr2 plays important roles in intestinal homeostasis. Agr2-/- intestine has decreased goblet cell Mucin 2, dramatic expansion of the Paneth cell compartment, abnormal Paneth cell localization, elevated endoplasmic reticulum (ER) stress, severe terminal ileitis and colitis. Cell culture experiments show that Agr2 expression is induced by ER stress, and that siRNA knockdown of Agr2 increases ER stress response. These studies implicate Agr2 in intestinal homeostasis and ER stress and suggest a role in the etiology of inflammatory bowel disease.
前梯度 2（AGR2）是一种蛋白质二硫键异构酶，作为发育调节剂、存活因子和炎症性肠病易感性基因，在多种细胞谱系的多种过程中发挥重要作用。在这里，我们使用种系和诱导型 Agr2-/- 小鼠表明 Agr2 在肠道稳态中发挥重要作用。Agr2-/- 肠道中的杯状细胞粘蛋白 2 减少，潘氏细胞区室显著扩张，潘氏细胞定位异常，内质网（ER）应激升高，末端回肠炎和结肠炎严重。细胞培养实验表明，Agr2 的表达受 ER 应激诱导，而 Agr2 的 siRNA 敲低会增加 ER 应激反应。这些研究表明 Agr2 参与肠道稳态和 ER 应激，并提示其在炎症性肠病发病机制中的作用。
