Disruption of Paneth and Goblet Cell Homeostasis and Increased Endoplasmic Reticulum Stress in Agr2-/- Mice

Overview

Journal Dev Biol

Publisher Elsevier

Specialties Biology
Reproductive Medicine

Date 2009 Dec 23

PMID 20025862

Citations 120

Authors

Fang Zhao

Robert Edwards

Diana Dizon

Kambiz Afrasiabi

Jennifer R Mastroianni

Mikhail Geyfman

Andre J Ouellette

Bogi Andersen

Steven M Lipkin

Affiliations

Soon will be listed here.

Abstract

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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