Intrinsic Autophagy Is Required for the Maintenance of Intestinal Stem Cells and for Irradiation-Induced Intestinal Regeneration

被引：109

作者：

Asano, Jumpei ^{[1
]}

Sato, Taku ^{[1
,4
]}

Ichinose, Shizuko ^{[2
]}

Kajita, Mihoko ^{[1
]}

Onai, Nobuyuki ^{[1
]}

Shimizu, Shigeomi ^{[3
]}

Ohteki, Toshiaki ^{[1
]}

机构：

[1] TMDU, Dept Biodef Res, Med Res Inst, Tokyo 1138510, Japan

[2] TMDU, Res Ctr Med & Dent Sci, Tokyo 1138510, Japan

[3] TMDU, Dept Pathol Cell Biol, Med Res Inst, Tokyo 1138510, Japan

[4] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol PRESTO, Kawaguchi, Saitama 3320012, Japan

来源：

CELL REPORTS | 2017年 / 20卷 / 05期

基金：

日本科学技术振兴机构;

关键词：

GENOME-WIDE ASSOCIATION; CROHN-DISEASE; PANETH CELLS; MITOCHONDRIA; EXPRESSION; CRYPT; DIFFERENTIATION; IDENTIFICATION; ATG16L1; ABSENCE;

D O I：

10.1016/j.celrep.2017.07.019

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Autophagy is a lysosomal degradation pathway with important roles in physiological homeostasis and disease. However, the role of autophagy in intestinal stem cells (ISCs) is unclear. Here, we show that intrinsic autophagy in ISCs is important for ISC homeostasis. Mice lacking autophagy protein 5 (ATG5) in intestinal epithelial cells (iECs) (Villin-Cre: Atg5(fl/fl), hereafter Atg5(Delta IEC) mice) or in all iECs except Paneth cells (Ah-Cre: Atg5(fl/fl) mice) had significantly fewer ISCs than did control mice and showed impaired ISC-dependent intestinal recovery after irradiation. Crypt ISCs from Atg5(Delta IEC) mice had significantly higher reactive oxygen species (ROS) levels than did those from control mice. A ROS-inducing reagent decreased the ISC number and impaired ISC regenerative capacity ex vivo, and treating Atg5(Delta IEC) mice with an antioxidant rescued their defects. Our results show that intrinsic autophagy supports ISC maintenance by reducing excessive ROS. Optimizing autophagy may lead to autophagy-based therapies for intestinal injuries.

引用

页码：1050 / 1060

页数：11

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