Disruption of Paneth and goblet cell homeostasis and increased endoplasmic reticulum stress in Agr2-/- mice.

Disruption of Paneth and goblet cell homeostasis and increased endoplasmic reticulum stress in Agr2-/- mice.
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DOI:
10.1016/j.ydbio.2009.12.008
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发表时间:
2010-02-15
影响因子:
2.7
通讯作者:
Lipkin, Steven M.
Lipkin, Steven M.
中科院分区:
生物学3区
文献类型:
--
作者:
Zhao, Fang;Edwards, Robert;Dizon, Diana;Afrasiabi, Kambiz;Mastroianni, Jennifer R.;Geyfman, Mikhail;Ouellette, Andre J.;Andersen, Bogi;Lipkin, Steven M.

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前梯度2(AGR 2)是一种蛋白质二硫键异构酶,在多种细胞谱系的不同过程中发挥重要作用,作为发育调节因子,存活因子和炎症性肠病的易感基因。在这里,我们使用种系和诱导型Agr 2 −/−小鼠表明,Agr 2在肠道内稳态中起着重要作用。Agr 2 −/−肠具有杯状细胞粘蛋白2减少、潘氏细胞区室急剧扩张、潘氏细胞定位异常、内质网(ER)应激升高、严重末端回肠炎和结肠炎。细胞培养实验表明,Agr 2的表达是由ER应激诱导的,并且Agr 2的siRNA敲低增加了ER应激反应。这些研究表明Agr 2参与了肠道内稳态和ER应激,并提示其在炎症性肠病的病因学中发挥作用。
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.
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